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Mucosal associated invariant T (MAIT) cells are a population of evolutionarily conserved T cells, which express an invariant T cell receptor (TCR) and represent a significant subset of innate-like T cells in humans, yet their role in immunity is still emerging. Unlike conventional αβ T cells, MAIT cells are not restricted by MHC molecules, but instead uniquely recognize microbially derived vitamin metabolites presented by the MHC-I like molecule MR1. MAIT cells are enriched in mucosal sites and tissues including liver and adipose tissue where they are thought to play an important role in immunosurveillance and immunity against microbial infection. In addition to their putative role in antimicrobial immunity, recent research on MAIT cells, in particular IL-17 producing MAIT cells, has demonstrated their involvement in numerous chronic inflammatory conditions. In this review, we give an overview of the work to date on the function and subsets of MAIT cells. We also examine the role of IL-17 producing MAIT cells in chronic inflammatory diseases ranging from autoimmune conditions, metabolic diseases to cancer. Furthermore, we discuss the most recent findings from the clinic that might help deepen our understanding about the biology of MAIT cells., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: To identify inflammatory cell types by phenotypic analysis of the inflammatory cells in the induced sputum., Methods: This retrospective study included 1232 children and infants, who were assigned into mild/moderate groups (326) and severe group (602) by clinical symptom scores. Phenotypes of sputum inflammatory cells were analyzed using liquid-based thin-cytologic test and eosinophil-derived neurotoxin (EDN) was quantified by ELISA., Results: Blood eosinophil count, serum total IgE level, and allergen detection rate were significantly higher in the severe group. In the 905 cases of qualified sputum, 526 cases exhibited at least one type of inflammatory cells, including neutrophil (343, 65.2%), eosinophil (161, 30.6%), and mixed granulocytes (22, 4.2%). Levels of neutrophils and eosinophils were significantly higher in the severe group than mild/moderate group, and eosinophil was predominant in the severe group. Serum EDN was 104.8 ± 39.4 μg/l in the eosinophil phenotype group, 112.6 ± 41.2 μg/l in the mixed group, 88.2 ± 36.6 μg/l in the neutrophil phenotype group, and 60.9 ± 34.6 μg/l in the paucigranulocytic phenotype group., Conclusion: Induced-sputum inflammatory cell count may be used to determine phenotype of wheezing. The criteria of classifying adult asthma could be applicable for children and infants.

Background: The small airways are an important site of inflammation in asthma. However, the relation between small airway dysfunction and clinical expression of asthma has hardly been studied. Aim: To investigate the association of small and large airway dysfunction with asthma symptoms and bronchial hyper-responsiveness (BHR). Methods: Fifty-eight patients with asthma were characterized with spirometry, body plethysmography, impulse oscillometry, alveolar and bronchial exhaled nitric oxide, and a methacholine provocation. Symptoms of nocturnal asthma, exercise-related symptoms, BHR symptoms, and respiratory symptoms were assessed with the Asthma Control Questionnaire and Bronchial Hyper-responsiveness Questionnaire. Perception of dyspnea was rated with the Borg score during the provocation test. Results: Small and large airway dysfunction did not associate with higher scores for nocturnal, exercise-related, or BHR symptoms. Only higher scores on wheezing were significantly associated with higher values of difference between R5 and R20 (R5-R20) (r = 0.367, P < 0.01) and AX (r = 0.354, /><0.0l). Lower FEF25-75% (P = 0.024) and higher R5-R20 (P = 0.003) values were independently associated with more severe BHR to methacholine, but not FEV! or R20 values. The increase in dyspnea during the methacholine provocation was strongly and independently correlated with the decrease in FEVj and reactance of the respiratory system at 5 Hertz. Conclusion: Small and large airway dysfunction poorly associate with asthma symptoms in our patients. However, deteriorations in small airway dysfunction are strongly related to an increase in dyspnea during bronchial provocation with methacholine. Small airway dysfunction contributes also independently to the clinical expression of asthma, as reflected by the severity of BHR. [ABSTRACT FROM AUTHOR]

Asthma is a chronic respiratory disease, characterized by airway obstruction and inflammation. Increasing evidence shows that the small airways contribute significantly to the clinical expression and severity of asthma. Traditionally, high levels of disease activity are thought to be necessary before symptoms occur in the small airways because of their large reserve capacity. However, this concept is being challenged and increasing evidence shows small airway disease to be associated with symptoms, disease severity, and bronchial hyper-responsiveness. Particle size and distribution are of key importance when developing inhaled treatments for small airway disease. The availability of small-particle aerosols such as HFA-ciclesonide and HFA-beclomethasone dipropionate ( HFA- BDP) enables a higher drug deposition into the peripheral lung and potentially provides additional clinical benefits compared with large-particle treatment. However, improved methods are needed to monitor and assess small airway disease and its response to treatment because conventional spirometry mainly reflects large airway function. This remains a challenging area requiring further research. The aim of the current manuscript is to review the clinical relevance of small airway disease and the implications for the treatment of asthma. [ABSTRACT FROM AUTHOR]

Background The incidence of asthma and obesity is increasing worldwide, and reports suggest that obese patients have more severe asthma. We investigated whether obese asthma patients have more severe airway obstruction and airway hyper-responsiveness and a different type of airway inflammation than lean asthmatics. Furthermore, we assessed the effect of obesity on corticosteroid treatment response. Methods Patient data from four well-documented asthma cohorts were pooled ( n = 423). We evaluated FEV1, bronchial hyper-responsiveness ( PC20) to either methacholine/histamine or adenosine 5′-monophosphate ( AMP) (differential) cell counts in induced sputum and blood and corticosteroid treatment response in 118 patients. Results At baseline, FEV1, PC20 methacholine or histamine, and PC20 AMP values were comparable in 63 obese ( BMI ≥30 kg/m2) and 213 lean patients ( BMI <25 kg/m2). Obese patients had significantly higher blood neutrophils. These higher blood neutrophils were only seen in obese women and not in obese men. After a two-week treatment with corticosteroids, we observed less corticosteroid-induced improvement in FEV1%predicted in obese patients than in lean patients (median 1.7% vs 6.3% respectively, P = 0.04). The percentage of sputum eosinophils improved significantly less with higher BMI ( P = 0.03), and the number of blood neutrophils increased less in obese than in lean patients (0.32 x103/μl vs 0.57 x103/μl, P = 0.046). Conclusions We found no differences in asthma severity between obese and nonobese asthmatics. Interestingly, obese patients demonstrated more neutrophils in sputum and blood than nonobese patients. The smaller improvement in FEV1 and sputum eosinophils suggests a worse corticosteroid treatment response in obese asthmatics. [ABSTRACT FROM AUTHOR]

Background The effects of smoking on asthma pathogenesis are complex and not well studied. We have shown recently that 3 weeks of smoking attenuates ovalbumin (OVA)-induced airway inflammation in mice and that 4–6 months of smoking induces emphysema in mice without airway inflammation. Effects of combined long-term smoking and OVA exposure have not been investigated so far. Objective To study whether long-term smoking affects progression of allergic airway inflammation and/or enhances the development of emphysema in mice. Methods Mice were sensitized to OVA and challenged with saline or OVA aerosols for 6 months. From 2 months onwards, mice were also exposed to air or smoke. Lung tissue was analysed for extent of inflammation, emphysema, remodelling and for cytokine levels, and serum for OVA-specific IgE levels. Results Chronic OVA exposure of 6 months resulted in a T helper type 2 (Th2)-type inflammation with increased levels of IL-4, IL-5, IL-6 and infiltration of eosinophils, CD4+ T cells, macrophages and plasma cells. Smoking induced a Th17-type of airway inflammation, characterized by neutrophils, macrophages, B cells and increased levels of IL-17, IL-6, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1. Concomittant smoking and OVA exposure resulted in inflammation similar to OVA exposure alone. OVA exposure increased IgE levels compared with saline exposure, and smoking did not further increase these levels. Conclusion We did not find evidence for increased inflammation, IgE levels or emphysema in mice with allergic airway inflammation after 4 months of smoking compared with non-smoking. However, a 4-month exposure to smoke alone did enhance neutrophilic airway inflammation characterized by high pulmonary IL-17 levels. A Th2 inflammatory environment due to OVA exposure may be one explanation as to why no further detrimental effects of smoking on allergic airway inflammation were found. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation. Although smoking cessation improves symptoms and the decline in lung Function in COPD, it is unknown whether bronchial inflammation in patients with established COPD varies with the duration of smoking cessation. Methods: 114 patients (99 men) with COPD of mean (SD) age 62 (8) years, a median (IQR) smoking history of 42 (31-55) pack years, no inhaled or oral corticosteroids, all current or ex-smokers (n = 42, quit >1 month, median cessation duration 3.5 years), post-bronchodilator FEV1 63 (9)% predicted, and FEV1/IVC 48 (9)% were studied cross sectionally. The numbers of subepithelial T lymphocytes (CD3, CD4, CD8), neutrophils, macrophages, eosinophils, mast cells, and plasma cells were measured in bronchial biopsy specimens (median (IQR)/0.1 mm²) using Fully automated image analysis. Results: Ex-smokers with COPD had higher CD3+, CD4+, and plasma cell numbers than current smokers with COPD (149 (88-225) v 108 (61-1 64), p=0.036 58 (32-90) v 40 (25-66), p=0.023; and 9.0 (5.5-20) v 7.5 (3.1-14), p=0.044, respectively), but no difference in other inflammatory cells. Short term ex-smokers (⩾3.5 years) had higher CD4+ and CD8+ cell numbers than current smokers (p = 0.017, p=0.023 respectively). Conversely, long term ex-smokers (quit 13.5 years) had lower CD8+ cell numbers than short term ex-smokers (p = 0.009), lower CD8/CD3 ratios than both current smokers and short-term ex-smokers (p=0.012, p=0.003 respectively), and higher plasma cell numbers than current smokers (p=0.003). Conclusions: With longer duration of smoking cessation, CD8 cell numbers decrease and plasma cell numbers increase. This indicates that bronchial T lymphocyte and plasma cell counts, but not other inflammatory cells, are related to duration of smoking cessation in patients with COPD. [ABSTRACT FROM AUTHOR]

Background In humans the prevalence of asthma is higher among females than among males after puberty. The reason for this phenomenon is not clear. Objective We tested the hypothesis that female mice are more susceptible to the development of allergic asthma than male mice and studied allergic immune responses in the lung. Methods We compared allergic airway inflammation, i.e. methacholine (MCh) responsiveness, serum IgE, and cytokines, and the number of the different leucocytes in lungs of male and female BALB/c mice, twice-sensitized to ovalbumin (OVA) and subsequently challenged with OVA (OVA-mice) or phosphate-buffered saline (PBS-mice) aerosols on days 24–26, 30, and 31. Results OVA challenge significantly increased MCh responsiveness, numbers of eosinophils, CD4+ T cells, CD4+/CD25+ T cells, B cells, and levels of Thelper (Th)2 cytokines, total, and OVA-specific IgE. There was, however, also an effect of gender, with female mice responding to OVA challenges with higher numbers of eosinophils, CD4+ T cells, B cells, and levels of IL-4, IL-13, IFN-γ, total, and OVA-specific IgE than male mice. In contrast, female PBS-mice had significantly lower percentages of regulatory CD4+/CD25+ T cells than males (females 4.2±0.2% vs. males 5.3±0.1% of CD4+ T cells, P<0.05). Conclusion Female mice develop a more pronounced type of allergic airway inflammation than male mice after OVA challenge. The reduced percentage of regulatory T cells in the lungs of female PBS-mice may indicate that the level of these cells in the lung during the sensitization phase is important for the development and/or progression of an allergic immune response after multiple OVA challenges. [ABSTRACT FROM AUTHOR]

Compared with the effects of chronic smoke exposure on lung function and airway inflammation, there are few data on the acute effects of smoking. A review of the literature identified 123 studies investigating the acute effects of cigarette smoking on inflammation and oxidative stress in human, animal, and in vitro models. An acute smoking model is a relatively easy and sensitive method of investigating the specific effects of cigarette smoke on oxidative stress and inflammation. Acute smoke exposure can result in tissue damage, as suggested by increased products of lipid peroxidation and degradation products of extracellular matrix proteins. Acute cigarette smoke has a suppressive effect on the number of eosinophils and several inflammatory cytokines, possibly due to the anti- inflammatory effect of carbon monoxide. An acute smoking model can supplement other ways of studying the effects of smoking and is an as yet underinvestigated method for intervention studies in smoking related diseases. [ABSTRACT FROM AUTHOR]

Bronchial hyper-responsiveness is usually measured with direct stimuli such as methacholine (MCh) or histamine. Adenosine 5′-monophosphate (AMP), which acts indirectly via the secondary release of mediators, is another stimulus to measure bronchial hyper-responsiveness. To investigate whether provocation with inhaled AMP itself initiates an inflammatory response resulting in an influx of eosinophils into the airway lumen. We have included 21 non-smoking atopic asthmatic subjects (mean FEV1 101% predicted, mean age 34 years). Each subject performed three sputum inductions on different days, at least seven days apart: one without previous provocation, one hour after PC20 methacholine, and one hour after PC20 AMP. After provocation with AMP, but not methacholine, the percentage of sputum eosinophils increased significantly (from 1.9±0.5% to 4.5±1% ( P<0.01) and 1.9±0.5% ( P=0.89)). No changes in the percentages of neutrophils, lymphocytes, macrophages, or bronchial epithelial cells were found. A provocation test with AMP leads to an increased percentage of sputum eosinophils. This observation cannot be explained by a non-specific response of the airways to a vigorous bronchoconstriction, since methacholine had no effect on inflammatory cells. [ABSTRACT FROM AUTHOR]

Evaluates bronchial hyperresponsiveness (BHR) to the indirect stimuli adenosine and hypertonic saline (HS) with respect to their mechanism of action and their relationship to eosinophilic bronchial inflammation. Role played by mast-cell derived histamine in adenosine-induced bronchoconstriction; Development of bronchial challenge with HS as a surrogate measure for exercised-induced bronchoconstriction; Assessment of the sensitivity and specificity of BHR.

Focuses on development of airflow limitation in chronic obstructive pulmonary disease. Close relationship between the presence of inflammatory cells and their mediators and airway remodelling; Presence of increased amounts of sputum; Bronchoalveolar lavage fluid; Airway wall inflammation; Exaggerated response of the airways to pharmacological, chemical, physical or physiological stimuli.

Introduction: Allergic airway diseases are one of the serious health problems in worldwide and allergic airway inflammation is a prerequisite led to the exacerbated situation such as mucus hypersecretion, epithelial barrier damage and microbiota dysbiosis. Because of side effects and low efficiencies of current therapeutics, the need for novel alternatives has been urged. Probiotics in which have diverse and beneficial modulatory effects have been applied to the airway inflammation model and the underlying mechanism needs to be investigated. Methods: We aimed to evaluate whether our target strain, Lactiplantibacillus plantarum APsulloc331261 (GTB1TM) isolated from green tea, can ameliorate allergic airway inflammation in mice and to figure out the mechanism. We induced allergic airway inflammation to mice by ovalbumin (OVA) and administered GTB1 orally and the immune and epithelial barrier markers were assessed. The gut metabolite and microbiota were also analysed, and the in vitro cell-line experiment was introduced to confirm the hypothesis of the study. Results: GTB1 ameliorated type 2 inflammation and suppressed mucin hypersecretion with the inhibition of MUC5AC in inflamed mice. Moreover, GTB1 increased the butyrate production and the relative abundance of butyrate producer, Clostridium cluster IV. We assumed that butyrate may have a potential role and investigated the effect of butyrate in mucin regulation via human airway epithelial cell line, A549. Butyrate significantly reduced the gene expression of MUC5AC in A549 cells suggesting its regulatory role in mucus production. Conclusion: Therefore, our study demonstrates that the oral administration of GTB1 can ameliorate allergic airway inflammation and mucin hypersecretion by butyrate production. [ABSTRACT FROM AUTHOR]

Background: Asthma is a prominent non-communicable inflammatory disease that affects both children and the elderly. Younger people are more prone to asthma, and most prescribed anti-asthmatic medicines relieve symptoms but do not cure the condition completely. We investigated the ability of a phytochemical plumbagin to alleviate ovalbumin (OVA)-induced asthma in BALB/c mice. Materials and Methods: The allergic asthma-induced mice were treated with two different doses of 25 and 50 mg/kg bwt plumbagin, and to compare the efficacy of plumbagin, a standard drug dexamethasone treatment was given. OVA-specific IgE and eotaxin were quantified to determine the induction of asthma and the inhibitory role of plumbagin. Total leukocyte and differential count were done to assess the effect of plumbagin on inflammatory cells. Inflammatory cytokines inducing both atopic and non-atopic asthma were quantified to examine the efficacy of plumbagin against allergic and non-allergic-induced asthma. Nitric oxide (NO) and myeloperoxidase activity were measured to investigate the anti-asthmatic potential of plumbagin. The antioxidant potency of plumbagin was assessed by quantifying the levels of antioxidants and the oxidative stress marker malondialdehyde. Lung weight index and histopathological analysis of lung tissue were done to confirm the ameliorative potency of plumbagin against OVA allergen-induced asthma. Results: Plumbagin treatment significantly decreased the status of OVA-specific IgE and eotaxin, thereby prevented the eosinophilic infiltration. It also inhibited the synthesis of both atopic and non-atopic inducing inflammatory cytokines. Plumbagin treatment also increased the levels of antioxidants and prevented the lung tissue damage, which was evidenced with our histopathology study of lung tissue. Conclusion: Overall, our finding confirms that plumbagin is persuasively alleviated OVA allergen-induced asthma complications in mice model and may be an alternative for currently available anti-asthmatic drugs. [ABSTRACT FROM AUTHOR]

Background: Allergic airway disease (AAD) is a growing concern in industrialized nations and can be influenced by fungal exposures. Basidiomycota yeast species such as Cryptococcus neoformans are known to exacerbate allergic airway disease; however, recent indoor assessments have identified other Basidiomycota yeasts, including Vishniacozyma victoriae (syn. Cryptococcus victoriae), to be prevalent and potentially associated with asthma. Until now, the murine pulmonary immune response to repeated V. victoriae exposure was previously unexplored. Objective: This study aimed to compare the immunological impact of repeated pulmonary exposure to Cryptococcus yeasts. Methods: Mice were repeatedly exposed to an immunogenic dose of C. neoformans or V. victoriae via oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and lungswere collected to examine airway remodeling, inflammation,mucous production, cellular influx, and cytokine responses at 1 day and 21 days post final exposure. The responses to C. neoformans and V. victoriae were analyzed and compared. Results: Following repeated exposure, both C. neoformans and V. victoriae cells were still detectable in the lungs 21 days post final exposure. Repeated C. neoformans exposure initiatedmyeloid and lymphoid cellular infiltration into the lung thatworsened over time, as well as an IL-4 and IL-5 response compared to PBS-exposed controls. In contrast, repeated V. victoriae exposure induced a strong CD4+ T cell-driven lymphoid response that started to resolve by 21 days post final exposure. Discussion: C. neoformans remained in the lungs and exacerbated the pulmonary immune responses as expected following repeated exposure. The persistence of V. victoriae in the lung and strong lymphoid response following repeated exposure were unexpected given its lack of reported involvement in AAD. Given the abundance in indoor environments and industrial utilization of V. victoriae, these results highlight the importance to investigate the impact of frequently detected fungal organisms on the pulmonary response following inhalational exposure. Moreover, it is important to continue to address the knowledge gap involving Basidiomycota yeasts and their impact on AAD. [ABSTRACT FROM AUTHOR]

Summary Background There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response. Aim We wanted to determine whether we could actually predict a favourable response to inhaled corticosteroids in individual patients. Methods One hundred and twenty patients with unstable asthma were treated with either prednisolone 30 mg/day, fluticasone propionate 1000 µg/day b.i.d. or fluticasone propionate 250 µg/day b.i.d., both via Diskhaler. They were treated during 2 weeks, in a double-blind, parallel group, double dummy design. We measured eosinophils and ECP in blood and sputum, and exhaled nitric oxide as inflammatory parameters before and after 2 weeks in order to predict the changes in forced expiratory volume in 1 s (FEV1 ), provocative concentration of methacholine causing a 20% fall in FEV 1 (PC 20 Mch), and asthma quality of life (QOL). Secondly, to test whether these results were applicable in clinical practice we determined the individual prediction of corticosteroid response. Results We found that changes in FEV1 , PC 20 Mch and QOL with corticosteroids were predominantly predicted by their respective baseline value and to a smaller extent by eosinophils in blood or sputum. ECP, measured in blood or sputum, was certainly not better than eosinophils in predicting clinical response to corticosteroids. Smoking status was an additional predictor for change in FEV 1 , but not for change in PC 20 Mch or QOL. Prediction of a good clinical response was poor. For instance, high sputum eosinophils (≥ 3%) correctly predicted an improvement in PC 20 Mch in only 65% of the patients. Conclusion Our findings show that baseline values of the clinical parameters... [ABSTRACT FROM AUTHOR]

Background: Allergic airway disease (AAD) is a growing concern in industrialized nations and can be influenced by fungal exposures. Basidiomycota yeast species such as Cryptococcus neoformans are known to exacerbate allergic airway disease; however, recent indoor assessments have identified other Basidiomycota yeasts, including Vishniacozyma victoriae (syn. Cryptococcus victoriae), to be prevalent and potentially associated with asthma. Until now, the murine pulmonary immune response to repeated V. victoriae exposure was previously unexplored. Objective: This study aimed to compare the immunological impact of repeated pulmonary exposure to Cryptococcus yeasts. Methods: Mice were repeatedly exposed to an immunogenic dose of C. neoformans or V. victoriae via oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and lungs were collected to examine airway remodeling, inflammation, mucous production, cellular influx, and cytokine responses at 1 day and 21 days post final exposure. The responses to C. neoformans and V. victoriae were analyzed and compared. Results: Following repeated exposure, both C. neoformans and V. victoriae cells were still detectable in the lungs 21 days post final exposure. Repeated C. neoformans exposure initiated myeloid and lymphoid cellular infiltration into the lung that worsened over time, as well as an IL-4 and IL-5 response compared to PBS-exposed controls. In contrast, repeated V. victoriae exposure induced a strong CD4+ T cell-driven lymphoid response that started to resolve by 21 days post final exposure. Discussion: C. neoformans remained in the lungs and exacerbated the pulmonary immune responses as expected following repeated exposure. The persistence of V. victoriae in the lung and strong lymphoid response following repeated exposure were unexpected given its lack of reported involvement in AAD. Given the abundance in indoor environments and industrial utilization of V. victoriae, these results highlight the importance to investigate the impact of frequently detected fungal organisms on the pulmonary response following inhalational exposure. Moreover, it is important to continue to address the knowledge gap involving Basidiomycota yeasts and their impact on AAD. [ABSTRACT FROM AUTHOR]

Heme oxygenase (HO) enzymes are responsible for the main oxidative step in heme degradation, generating equimolar amounts of free iron, biliverdin and carbon monoxide. HO-1 is induced as a crucial stress response protein, playing protective roles in physiologic and pathological conditions, due to its antioxidant, anti-apoptotic and anti-inflammatory effects. The mechanisms behind HO-1-mediated protection are being explored by different studies, affecting cell fate through multiple ways, such as reduction in intracellular levels of heme and ROS, transcriptional regulation, and through its byproducts generation. In this review we focus on the interplay between HO-1 and immune-related signaling pathways, which culminate in the activation of transcription factors important in immune responses and inflammation. We also discuss the dual interaction of HO-1 and inflammatory mediators that govern resolution and tissue damage. We highlight the dichotomy of HO-1 in innate and adaptive immune cells development and activation in different disease contexts. Finally, we address different known anti-inflammatory pharmaceuticals that are now being described to modulate HO-1, and the possible contribution of HO-1 in their anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Background and aim: Allergic asthma is a complex inflammatory disease involving type 2 innate lymphoid cells, type 2 T helper cells, macrophages, and eosinophils. The disease is characterized by wheezing, dyspnea, coughing, chest tightness and variable airflow limitation for which there is no cure and is symptomatically treated with inhaled corticosteroids and β2-agonists. Molecular mechanisms underlying its complex pathogenesis are not fully understood. However, 8-oxoguanine DNA glycosylase-1 (OGG1), a DNA repair protein may play a central role, as OGG1 deficiency decreases both innate and allergic inflammation. Methods: Using a murine ovalbumin (OVA) model of allergic airway inflammation we assessed the utility of an inhibitor of OGG1 (TH5487) in this disease context. Cytokines and chemokines, promoting immune cell recruitment were measured using a 23-multiplex assay and Western blotting. Additionally, immune cell recruitment to bronchi was measured using flow cytometry. Histological analyses and immunofluorescent staining were used to confirm immune cell influx and goblet cell hyperplasia of the airways. A PCR array was used to assess asthma-related genes in murine lung tissue following TH5487 treatment. Finally, airway hyperresponsiveness was determined using in vivo lung function measurement. Results: In this study, administration of TH5487 to mice with OVA-induced allergic airway inflammation significantly decreased goblet cell hyperplasia and mucus production. TH5487 treatment also decreased levels of activated NF-κB and expression of proinflammatory cytokines and chemokines resulting in significantly lower recruitment of eosinophils and other immune cells to the lungs. Gene expression profiling of asthma and allergy-related proteins after TH5487 treatment revealed differences in several important regulators, including down regulation of Tnfrsf4, Arg1, Ccl12 and Ccl11, andupregulation of the negative regulator of type 2 inflammation, Bcl6. Furthermore, the gene Clca1 was upregulated following TH5487 treatment, which should be explored further due to its ambiguous role in allergic asthma. In addition, the OVA-induced airway hyperresponsiveness was significantly reduced by TH5487 treatment. Conclusion: Taken together, the data presented in this study suggest OGG1 as a clinically relevant pharmacological target for the treatment of allergic inflammation. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a pulmonary illness with a high burden of morbidity and mortality around the world. Chronic lung diseases also represent lifethreatening situations. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a type of long non-coding RNA (lncRNA) and is highly abundant in lung tissues. MALAT1 can function as a competitive endogenous RNA (ceRNA) to impair the microRNA (miRNA) inhibition on targeted messenger RNAs (mRNAs). In this review, we summarized that MALAT1 mainly participates in pulmonary cell biology and lung inflammation. Therefore, MALAT1 can positively or negatively regulate ALI and chronic lung diseases (e.g., chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), pulmonary fibrosis, asthma, and pulmonary hypertension (PH)). Besides, we also found a MALAT1-miRNA-mRNA ceRNA regulatory network in acute and chronic lung diseases. Through this review, we hope to cast light on the regulatory mechanisms of MALAT1 in ALI and chronic lung disease and provide a promising approach for lung disease treatment. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a widespread disease associated with high rates of disability and mortality. COPD is characterized by chronic inflammation in the bronchi as well as systemic inflammation, which contributes significantly to the clinically heterogeneous course of the disease. Lipid metabolism disorders are common in COPD, being a part of its pathogenesis. High-density lipoproteins (HDLs) are not only involved in lipid metabolism, but are also part of the organism's immune and antioxidant defense. In addition, HDL is a versatile transport system for endogenous regulatory agents and is also involved in the removal of exogenous substances such as lipopolysaccharide. These functions, as well as information about lipoprotein metabolism disorders in COPD, allow a broader assessment of their role in the pathogenesis of heterogeneous and comorbid course of the disease. [ABSTRACT FROM AUTHOR]

Apoptosis of cells at the site of infection is a requirement for shutdown of inflammatory signaling, avoiding tissue damage, and preventing progression of sepsis. Puma+/+ and Puma-/- mice were challenged with TIGR4 strain pneumococcus and cytokines were quantitated from lungs and blood using a magnetic bead panel analysis. Puma-/- mice exhibited higher lung and blood cytokine levels of several major inflammatory cytokines, including IL-6, G-CSF, RANTES, IL-12, IFN-ϒ, and IP-10. Puma-/- mice were more susceptible to bacterial dissemination and exhibited more weight loss than their wild-type counterparts. RNA sequencing analysis of whole pulmonary tissue revealed Puma-dependent regulation of Nrxn2 , Adam19 , and Eln. Enrichment of gene ontology groups differentially expressed in Puma-/- tissues were strongly correlated to IFN-β and -ϒ signaling. Here, we demonstrate for the first time the role of Puma in prohibition of the cytokine storm during bacterial pneumonia. These findings further suggest a role for targeting immunomodulation of IFN signaling during pulmonary inflammation. Additionally, our findings suggest previously undemonstrated roles for genes encoding regulatory and binding proteins during the early phase of the innate immune response of pneumococcal pneumonia. [ABSTRACT FROM AUTHOR]

Objective. To explore more efficient treatments for chronic obstructive pulmonary disease (COPD), effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) and electroacupuncture were tested on rats with COPD, and silent information regulator transcript-1 (SIRT1)/nuclear factor-kappaB (NF-κB) signaling was further investigated to interpret the therapy. Methods. In total, 70 rats were randomly divided into control (Control), model (Model), aminophylline (APL), ECC-BYF III, electroacupuncture (EA), ECC-BYF III+EA, and sham electroacupuncture (SA) groups. Cigarette smoke exposure combined with repeated bacterial infections was used to establish COPD models in 1–12 weeks. From 13 to 20 weeks, the ECC-BYF III and APL groups received corresponding drugs; the EA group received electroacupuncture therapy, wherein Dazhui (GV 14), Feishu (BL 13), and Shenshu (BL 23) points were selected; the ECC-BYF III+EA group received ECC-BYF III intragastrically combined with electroacupuncture; and the SA group received simulated electroacupuncture (nonacupoint). Pulmonary function, pulmonary histopathology, the expressions of SIRT1/NF-κB signaling, and inflammation-related mRNA and protein were detected. Results. Significant deterioration was observed in pulmonary function and pulmonary histopathology in rats with COPD (P < 0.01), and inflammatory state was illustrated by increased levels of interleukin- (IL-) 6 and tumor necrosis factor alpha (TNF-α) and decreased levels of IL-10 (P < 0.01). After the intervention of APL, ECC-BYF III, EA, and ECC-BYF III+EA, both pulmonary function and pulmonary histopathology were improved (P < 0.05 and P < 0.01), whereas the levels of IL-6 and TNF-α were decreased and IL-10 was increased (P < 0.05 and P < 0.01). Additionally, the mRNA expressions of IL-6, TNF-α, NF-κB, and acetylated NF-κBp65 (Ac-NF-κB) were noted to decrease, and SIRT1 and IL-10 were increased (P < 0.05 and P < 0.01); the protein expression of SIRT1 was upregulated, and NF-κBp65 and Ac-NF-κB were downregulated (P < 0.05 and P < 0.01). The effect of ECC-BYF III+EA was better in terms of improving pulmonary function and alleviating inflammation than that of the other treatment groups (P < 0.01 and P < 0.05). Conclusions. ECC-BYF III, electroacupuncture, and their combination can suppress inflammation, among which the combination therapy has been proven to be the most effective treatment, and the mechanism may be involved in activating SIRT1/NF-κB signaling. [ABSTRACT FROM AUTHOR]

Climate change‐related disasters have drawn increased attention to the impact of air pollution on health. 122 children ages 9–11 years old, M(SD) = 9.91(.56), participated. Levels of particulate matter (PM2.5) near participants' homes were obtained from the Environmental Protection Agency. Cytokines were assayed from 100 child serum samples: IL‐6, IL‐8, IL‐10, and TNFα. Autonomic physiology was indexed by pre‐ejection period (PEP), respiratory sinus arrhythmia (RSA), cardiac autonomic regulation (CAR), and cardiac autonomic balance (CAB). IL‐6 was positively related to daily PM2.5 (r =.26, p =.009). IL‐8 was negatively associated with monthly PM2.5 (r = −.23, p =.02). PEP was positively related to daily (r =.29, p =.001) and monthly PM2.5 (r =.18, p =.044). CAR was negatively associated with daily PM2.5 (r = −.29, p =.001). IL‐10, TNFα, RSA, and CAB were not associated with PM2.5. Air pollution may increase risk of inflammation in children. [ABSTRACT FROM AUTHOR]

Allergic diseases represent a global burden. Although the patho-physiological mechanisms are still poorly understood, epithelial barrier dysfunction and Th2 inflammatory response play a pivotal role. Barrier dysfunction, characterized by a loss of differentiation, reduced junctional integrity, and altered innate defence, underpins the pathogenesis of allergic diseases. Epithelial barrier impairment may be a potential therapeutic target for new treatment strategies Up now, monoclonal antibodies and new molecules targeting specific pathways of the immune response have been developed, and others are under investigation, both for adult and paediatric populations, which are affected by atopic dermatitis (AD), asthma, allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), or eosinophilic esophagitis (EoE). In children affected by severe asthma biologics targeting IgE, IL-5 and against IL-4 and IL-13 receptors are already available, and they have also been applied in CRSwNP. In severe AD Dupilumab, a biologic which inhibits both IL-4 and IL-13, the most important cytokines involved in inflammation response, has been approved for treatment of patients over 12 years. While a biological approach has already shown great efficacy on the treatment of severe atopic conditions, early intervention to restore epithelial barrier integrity, and function may prevent the inflammatory response and the development of the atopic march. [ABSTRACT FROM AUTHOR]

Background: Environmental factors, such as oxidative stress, have the potential to modify the epigenetic landscape of cells. We have previously shown that DNA methyltransferase (DNMT) activity can be inhibited by sublethal doses of hydrogen peroxide (H2O2). However, site-specific changes in DNA methylation and the reversibility of any changes have not been explored. Using bead chip array technology, differential methylation was assessed in Jurkat T-lymphoma cells following exposure to H2O2. Results: Sublethal H2O2 exposure was associated with an initial genome-wide decrease in DNA methylation in replicating cells, which was largely corrected 72 h later. However, some alterations were conserved through subsequent cycles of cell division. Significant changes to the variability of DNA methylation were also observed both globally and at the site-specific level. Conclusions: This research indicates that increased exposure to H2O2 can result in long-term alterations to DNA methylation patterns, providing a mechanism for environmental factors to have prolonged impact on gene expression. [ABSTRACT FROM AUTHOR]

Nickel nanoparticles (NiNPs) are increasingly used in nanotechnology applications, yet information on sex differences in NiNP-induced lung disease is lacking. The goal of this study was to explore mechanisms of susceptibility between male and female mice after acute or subchronic pulmonary exposure to NiNPs. For acute exposure, male and female mice received a single dose of NiNPs with or without LPS by oropharyngeal aspiration and were necropsied 24 h later. For subchronic exposure, mice received NiNPs with or without LPS six times over 3 weeks prior to necropsy. After acute exposure to NiNPs and LPS, male mice had elevated cytokines (CXCL1 and IL-6) and more neutrophils in bronchoalveolar lavage fluid (BALF), along with greater STAT3 phosphorylation in lung tissue. After subchronic exposure to NiNPs and LPS, male mice exhibited increased monocytes in BALF. Moreover, subchronic exposure of male mice to NiNP only induced higher CXCL1 and CCL2 in BALF along with increased alveolar infiltrates and CCL2 in lung tissue. STAT1 in lung tissue was induced by subchronic exposure to NiNPs in females but not males. Males had a greater induction of IL-6 mRNA in liver after acute exposure to NiNPs and LPS, and greater CCL2 mRNA in liver after subchronic NiNP exposure. These data indicate that susceptibility of males to acute lung inflammation involves enhanced neutrophilia with increased CXCL1 and IL-6/STAT3 signaling, whereas susceptibility to subchronic lung inflammation involves enhanced monocytic infiltration with increased CXCL1 and CCL2. STAT transcription factors appear to play a role in these sex differences. This study demonstrates sex differences in the lung inflammatory response of mice to NiNPs that has implications for human disease. [ABSTRACT FROM AUTHOR]

Introduction: Although the major alterations associated with asthma are related to the airways, there is also evidence of the importance of peribronchial vascular inflammation and remodeling in its pathophysiology. Objectives: To determine the effects of anti-IL-17 therapy on peribronchial vessels of an asthma model exacerbated by lipopolysaccharide. Methods: We evaluated several factors, including lung function, inflammation, oxidative stress, vascular remodeling, and signaling pathways present in the peribronchial vessels of 66 male BALB/c mice exposed to ovalbumin and treated (or not) treated with anti-IL-17. Twenty-four hours before the end of the experimental protocol, groups of sensitized animals (OVA–LPS and OVA–LPS anti-IL-17) also received LPS. Results: The OVA–LPS-anti-IL-17 group presented a decrease in several factors [airway resistance and elastance, bronchoalveolar lavage fluid (BALF) cell counts, inflammatory response, eosinophils, TSLP, IL-33, TARC, TNF-α, CD4+, CD8+, IL-4, IL-6, IL-10, IL-17, and VEGF positive cells/104μm2, peribronchovascular edema, and angiogenesis], including remodeling (MMP-9, MMP-12, TIMP-1 and TGF- β positive cells and volume fraction of collagen fibers I, collagen fibers III, collagen fibers V, decorin, lumican, actin, biglycan, fibronectin, and integrin), oxidative stress (iNOS positive cells and volume fraction of PGF2 α), and signaling pathways (FoxP3), as well as dendritic cells, NF-kB, ROCK-1, ROCK-2, STAT-1, and phosphor-STAT1-positive cells compared to OVA–LPS (p < 0.05). Conclusions: In this model of LPS-induced asthma exacerbation, IL-17 inhibition represents a promising therapeutic strategy, indicating the potential of bronchial vascular control of Th2 and Th17 responses and the activation of the remodeling and oxidative stress pathways, associated with the control of signaling pathways. [ABSTRACT FROM AUTHOR]

Background and Aim. Heme oxygenase-1 (HO-1) has been verified to play an important role in nonalcoholic steatohepatitis (NASH), but the mechanism remains unclear. In this study, we aimed to clarify whether induction of HO-1 reverses steatofibrosis via suppression of the Wnt signaling pathway and to explore the potential mechanism of HO-1 on NASH-related liver fibrosis. Methods. Mice were fed with a methionine-choline-deficient (MCD) diet for 8 weeks to induce steatohepatitis-related liver fibrosis and were treated with HO-1 inducer Hemin and inhibitor ZnPP. Mouse sera were collected for the biochemical analysis, and livers were obtained for further histological observation and gene expression analysis. HSC-T6 cells were cultured for the in vitro study and were administrated with Hemin and si-HO-1 to induce or inhibit the expression of HO-1. qPCR and Western blot were used to assess the mRNA and protein levels of genes. Results. MCD-fed mice developed marked macrovesicular steatosis, focal necrosis, and inflammatory infiltration and pericellular fibrosis in liver sections. Administration of Hemin could significantly ameliorate the severity of steatosis, inflammation, and fibrosis and also could decrease the serum ALT and AST. We demonstrated that HO-1 induction was able to downregulate the key regulator of the canonical Wnt pathway Wnt1 and the noncanonical Wnt pathway Wnt5a. The downstream factors of the Wnt pathway β-catenin and NFAT5 were inhibited by Hemin, but GSK-3β was upregulated compared to the MCD group, which were consistent with the in vitro study. Hemin markedly inhibited the TGF-β1/Smad signaling pathway in both in vivo and in vitro studies. Conclusion. Our study demonstrated that HO-1 inhibited the activation of canonical and noncanonical Wnt signaling pathways in NASH-related liver fibrosis. Thus, these results may suggest a new therapeutic strategy for NASH-related liver fibrosis. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?What is the mechanism of wheat‐induced pulmonary inflammation and how does a hydrazide derivative modulate it?What is the main finding and its importance?A hydrazide derivative significantly reduced wheat‐induced pulmonary inflammation in a rat model mainly by down‐regulating inflammatory cell infiltration, pathological lesions in the lungs and the level of pro‐inflammatory cytokines, COX‐1, COX‐2 and T‐cell proliferation. We investigated the ameliorative anti‐inflammatory effect of a previously synthesized hydrazide derivative (N′‐(4‐methoxybenzylidene)‐6‐(4‐chlorophenyl)‐3‐methyl‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐4‐carbohydrazide; MD) as an immunomodulator in a newly developed allergen‐induced pulmonary inflammation (AIPI) rat model. Wheat and thresher dust were used as allergens to induce pulmonary inflammation while MD was used to reverse the inflammatory response. Blood and bronchoalveolar lavage fluid (BALF) were collected after killing the rats and inflammatory cells were counted. Histological analysis of lung airways was carried out by haematoxylin and eosin and periodic acid–Schiff staining while the level of total serum IgE, interleukin (IL)‐4, IL‐5 and cyclooxygenase (COX)‐1 in BALF and in vitro T‐cell proliferation in spleen were measured through enzyme‐linked immunosorbent assay. mRNA expression level of IL‐4, IL‐5, IL‐13, transforming growth factor β (TGF‐β), interferon‐γ, tumour necrosis factor α, COX‐1 and COX‐2 was evaluated by qRT‐PCR. A liver and kidney function test was used to observe any toxic impact of MD. The results indicated that 2 mg of wheat and thresher dust led to higher levels of inflammatory cytokines in the blood, BALF and lung airways of rats. MD potentially down‐regulated the inflammatory cell infiltration in BALF and pathological lesions in the lung airways of AIPI rats. MD significantly suppressed the elevated total serum IgE, along with IL‐4, IL‐5, IL‐13, TGF‐β, COX‐1 and COX‐2 mRNA expression and T‐cell proliferation in spleen. In conclusion, MD at 10 mg kg−1 exhibited a significant reduction in all the markers in both wheat‐ and thresher dust‐induced pulmonary inflammation mainly by inhibiting pro‐inflammatory cytokine production and T‐cell proliferation. The data suggest that inhibition of the T‐cell response may be responsible for the modulative effect of MD in an AIPI rat model. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether there was an association between chronic periodontitis (CP) and reduced respiratory function. Methods: A group of dentate 58‐ to 72‐year‐old men in Northern Ireland had a comprehensive periodontal examination. Parallel to the periodontal examination, participants completed questionnaires gathering information on their medical history, social circumstances, demographic background and tobacco use. A physical examination assessed anthropometric measures. Fasting blood samples were obtained and analysed for high‐sensitivity C‐reactive protein (hs‐CRP). Spirometry measures were performed using a wedge bellows spirometer (Vitalograph S Model). The primary outcome variable of interest was the percentage predicted forced expiratory volume in one‐second (% predicted FEV1). Analysis included multiple linear regression with adjustment for various confounders and a regression‐based mediation analysis. Results: A total of 1,380 men were included in the analysis. The mean age was 63.7 years (SD 3.0). Multiple linear regression analysis showed that a doubling in mean clinical attachment loss (CAL) equated to a −3.33% (95% CI: −4.80, −1.86), p < 0.001 change in % predicted FEV1 after adjustment for all other potential confounding variables. Systemic inflammation, as measured by hs‐CRP, only accounted for a minor mediating pathway effect (9%). Conclusions: In this homogenous group of dentate men, CP was significantly associated with a reduced respiratory function. [ABSTRACT FROM AUTHOR]

Growing black carbon (BC) emission has become one of the major urgent environmental issues facing human beings. Usually, BC or BC‐containing carbon nanoparticles (CNPs) were recognized as non‐directly toxic components of atmospheric particulate matter. However, epidemiology studies have provided much evidence of the associations of exposure of particulate‐containing carbon particles with cardiovascular diseases. There are still no related studies to support the epidemiological conclusions. Hence, in this article we exposed adult zebrafish to CNPs for 60 days, and then explored the heart location and potential adverse effects on cardiac tissues of these nanosized carbon particles. Our results first showed direct visualization of cardiac endothelial uptake and heart deposition of CNPs in zebrafish. In addition, CNPs caused significant ultrastructural alterations in myocardial tissue and induced the expression of inflammatory cytokines in a dose‐dependent manner, resulting in sub‐endocardial inflammation and cell apoptosis. Moreover, our data demonstrated the perturbations caused by CNPs on DNA methylation, suggesting that DNA methylome remodeling might play a critical role in CNP‐induced cardiotoxicity in zebrafish heart. Therefore, this study not only proved a laboratory link between CNP exposure and cardiotoxicity in vivo, but also indicated a possible toxicity mechanism involved. Prolonged exposure to low concentrations of CNPs induced cardiac inflammation and cell apoptosis. We first showed direct visualization of cardiac endothelial uptake of CNPs. Heart distribution of CNPs caused DNA methylome remodeling, which was associated with inflammation‐related gene expression and apoptosis. [ABSTRACT FROM AUTHOR]

Background: Estrogen has been suggested to play a protective role against airway inflammations, such as asthma. In these processes, the inflammasome nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) partly accounts for the activation of pro-inflammatory factors. The aim of the present study was to investigate whether NLRP3 was involved in the protective effect of estrogen against allergic airway inflammation. Methods: An ovariectomy was performed on female C57BL/6 mice; some were sham-operated (sham). We then sensitized and challenged them with ovalbumin (OVA) to establish an airway inflammation model. Meanwhile, some mice were treated with 17β-estradiol (E2) for 28 days. Results: The expression of NLRP3 inflammasome and its downstream products, caspase-1 and the pro-inflammatory cytokine interleukin (IL)-1β (IL-1β), increased concomitantly with OVA-challenged airway inflammation and decreased with the expression of estrogen receptor β (ERβ). In addition, treating ovariectomized (OVX) mice with E2 dramatically ameliorated airway inflammation via such mechanisms as leukocyte recruitment, mucus production, and secretion of pro-inflammatory cytokines other than IL-18 in bronchoalveolar lavage (BAL) fluid (BALF). Furthermore, E2 suppressed both the mRNA expression and protein expression of NLRP3, caspase-1, and IL-1β. In summary, our study showed that NLRP3 inflammasome activation and pro-inflammatory cytokine production markedly increased in OVA-induced airway inflammation, and E2 effectively abrogated such inflammation by regulating the activation of NLRP3. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Does extracellular heat shock protein 70 (eHsp70) alter cigarette smoke extract (CSE)‐induced inflammatory responses in NCI‐H292 bronchial epithelial cells?What is the main finding and its importance?eHsp70 modulates inflammatory responses and TLR2, TLR4 and Hsp70 gene expression, and protects NCI‐H292 cells against CSE‐induced cytotoxicity. eHsp70 might be implicated in development of inflammatory diseases affected by cigarette smoke, such as COPD. One of the major risk factors for development of chronic obstructive pulmonary disease (COPD) is cigarette smoke. Extracellular Hsp70 (eHsp70) is increased in sera of COPD patients, and can act as damage‐associated molecular pattern (DAMP). In this study, we explored inflammatory parameters (cytokine concentrations, Toll‐like receptor (TLR) 2 and 4 and Hsp70 expression, mitogen‐activated protein kinases (MAPKs) and nuclear factor κB (NF‐κB) activation, and cytotoxicity) after exposure of bronchial‐epithelial NCI‐H292 cells to cigarette smoke extract (CSE) alone (2.5 and 15%) and in combinations with recombinant human (rh) Hsp70 (0.3, 1 and 3 μg ml−1). We applied specific MAPKs, NF‐κB and Hsp70 inhibitors to elucidate rhHsp70 inflammation‐associated responses. CSE alone and combinations of 15% CSE with rhHsp70 stimulated IL‐1α, IL‐6 and IL‐8 release. However, rhHsp70 applied with 2.5% CSE decreased secretion of cytokines indicating antagonistic effects. Individual and combined treatments with 2.5% CSE suppressed TLR2 expression. CSE at 15% induced TLR2 and TLR4 gene expression, whereas rhHsp70 abolished that effect. rhHsp70 and 15% CSE alone reduced, while their combination increased, intracellular Hsp70 mRNA level. CSE alone and in combination with rhHsp70 activated extracellular signal‐regulated kinase and p38 MAPKs, while inhibition of MAPKs, NF‐κB and Hsp70 attenuated IL‐6 and IL‐8 secretion. CSE at 15% reduced cell viability and induced apoptosis, as shown by MTS and caspases‐3/7 assays. CSE at 2.5% alone stimulated lactate dehydrogenase release, but cellular membrane integrity remained intact in co‐treatments with rhHsp70. rhHsp70 might modulate the inflammatory response of CSE and could also protect NCI‐H292 cells against CSE cytotoxicity. Those effects are implemented via MAPK and NF‐κB signalling pathways. [ABSTRACT FROM AUTHOR]

In developing youth, allergic asthma is the most common chronic condition, with 9%–10% of youth affected. Asthma onset during childhood and adolescence is further associated with other health issues, particularly psychiatric conditions. To understand causal mechanisms by which developmental asthma may lead to altered behavior, brain and health trajectories, we developed a mouse model of developmental allergic asthma. In the current study, we tested for potential long-term effects of developmental asthma on adult lung function and behavior and brain gene expression associated with emotion and stress regulation. We manipulated airway inflammation (AI) and methacholine (MCH)-induced bronchospasm (resulting in labored breathing, LB) in young male and female BALB/cJ mice and measured adult outcomes 3 months after final asthma manipulations. Results indicated that allergen exposure, used to cause AI, and which ended on post-natal day 56 (P56), led to persistent lung AI, mucus buildup and gene expression related to allergic asthma 3 months after final allergen exposure. In addition, at this same age, early allergen exposure led to altered brain gene expression related to stress regulation (prefrontal corticotropin releasing hormone receptor 1, Crhr1 and hippocampal glucocorticoid receptor, GR) and serotonin function (brainstem serotonin transporter, SERT). On the other hand, LB events during development led to altered anxiety-related behavior. Importantly, sex and pre-asthma fear-related behavior (ultrasonic vocalization, USV rates) modulated these adult outcomes. Asthma that develops during childhood/adolescence may have long-term impacts on emotion and stress regulation mechanisms, and these influences may be moderated by sex and pre-asthma temperament. [ABSTRACT FROM AUTHOR]

Cystic fibrosis is a genetic disease caused by mutations in the CFTR gene, whereas chronic obstructive pulmonary disease (COPD) is mainly caused by environmental factors (mostly cigarette smoking) on a genetically susceptible background. Although the etiology and pathogenesis of these diseases are different, both are associated with progressive airflow obstruction, airway neutrophilic inflammation, and recurrent exacerbations, suggesting common mechanisms. The airway epithelium plays a crucial role in maintaining normal airway functions. Major molecular and morphologic changes occur in the airway epithelium in both CF and COPD, and growing evidence suggests that airway epithelial dysfunction is involved in disease initiation and progression in both diseases. Structural and functional abnormalities in both airway and alveolar epithelium have a relevant impact on alteration of host defences, immune/inflammatory response, and the repair process leading to progressive lung damage and impaired lung function. In this review, we address the evidence for a critical role of dysfunctional airway epithelial cells in chronic airway inflammation and remodelling in CF and COPD, highlighting the common mechanisms involved in the epithelial dysfunction as well as the similarities and differences of the two diseases. [ABSTRACT FROM AUTHOR]

Asthma is a chronic respiratory disorder which is associated with airway inflammation. Environmental factors, in association with genetic susceptibility, play a critical role in asthma pathophysiology. Inhaled allergens, smoke exposure, indoor and outdoor air pollution are common triggers of asthma symptoms. Although the role of diet has clearly established mechanisms in diseases such as cardiovascular disease, type 2 diabetes, and cancer, it is not commonly identified as a causal factor in asthma. However, some dietary patterns, such as theWestern diet, which includes a high intake of refined grains, processed and red meats, and desserts, have pro-inflammatory effects. On the contrary, the Mediterranean diet, with high intake of fruits and vegetables has anti-inflammatory properties. The influence of food on asthma outcomes is of growing interest, but dietary habits of asthma patients are not commonly investigated in clinical practice. In this review, we focus on the impact of diet on asthma risk and asthma control. We also detail the influence of diet on obese patients with asthma. [ABSTRACT FROM AUTHOR]

Inflammation plays a key role in the initiation, progression, and clinical manifestation of atherosclerosis. Cigarette smoking is a risk factor for atherosclerosis and cardiovascular disease. The aim of the current study was to investigate the serum concentrations of 12 cytokines and growth factors (EGF, INF-γ, IL-1α/-1β/-2/-4/-6/-8/-10, MCP-1, TNF-α, and VEGF) in an Iranian population, including 192 smokers, comparing these values with concentrations in nonsmokers. One hundred and ninety-two cases were enrolled from the Mashhad University of Medical Sciences. Of these cases, 82 were cigarette smokers and 110 were nonsmokers. Sex and age were matched for the two groups. The serum concentration of 12 cytokines and growth factors were determined using EV-3513-cytokine-biochip arrays, by competitive chemiluminescence immunoassays. The level of serum MCP-1 was significantly (p < .001) lower in the female group of cigarette smokers (mean = 88.1 dL/ng), compared with nonsmokers (mean = 155.6 dL/ng). There were no significant differences for the other cytokines and growth factors between the groups. Our finding demonstrate the association of MCP-1 with cigarette smoking, supporting further studies in larger population on evaluating the role of cigarette smoking on pro-/anti-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Members of the whey acidic protein (WAP) or WAP four-disulfide-core (WFDC) family of proteins are a relatively under-explored family of low molecular weight proteins. The two most prominent WFDC proteins, secretory leukocyte protease inhibitor (SLPI) and elafin (or the precursor, trappin-2), have been shown to possess multiple functions including anti-protease, anti-bacterial, antiviral and anti-inflammatory properties. It is therefore of no surprise that both SLPI and elafin/trappin-2 have been developed as potential therapeutics. Given the abundance of SLPI and elafin/trappin-2 in the human lung, most work in the area of WFDC research has focused on the role of WFDC proteins in protecting the lung from proteolytic attack. In this review, we will outline the current evidence regarding the expanding role of WFDC protein function with a focus on WFDC activity in lung disease as well as emerging data regarding the function of some of the more recently described WFDC proteins. [ABSTRACT FROM AUTHOR]

Purpose:This study examined postexercise inflammatory and leukocyte responses in smokers and nonsmokers, as well as the effects of cigarette smoking on the acute postexercise inflammatory and leukocyte response in habitual smokers.Method:Eleven recreationally active male smokers and 11 nonsmokers matched for age and aerobic fitness were familiarized and underwent baseline fitness testing. Participants then completed 40 min of cycling at 50% peak aerobic workload. Smokers performed 2 randomized exercise sessions, including an acute postexercise smoking condition (2 cigarettes in 15 min of 12 mg tar and 1 mg nicotine) and a no-smoking condition, while nonsmokers performed 1 exercise session without smoking. Venous blood was obtained preexercise and postexercise for analysis of interleukin (IL)-6, IL-1 receptor antagonist (ra), tumor necrosis factor-alpha (TNF-α), and c-reactive protein (CRP).Results:No differences existed between groups for resting CRP (d = 0.25–0.46;p = .374–.617). Despite no baseline difference (d = 0.03–0.07;p = .141–.70), exercise-induced increases were observed for IL-1 ra in smokers (d = 0.50;p = .024–.033), which was not observed in the never-smoker group. No between-group difference was observed for IL-6 across all points (d = 0.09–0.5;p = .102–.728); however, all groups observed significant within-group change (d = 0.27–1.09;p = .001–.042). Further, TNF-α for smokers smoking was elevated above both smokers not smoking and nonsmokers at baseline and across the protocol (d = 1.20–1.80;d = 0.20–1.0;p = .001–.035). Additionally, a marked postexercise increase in leukocyte and neutrophil concentrations was evident in smokers smoking compared with nonsmokers and smokers not smoking as indicated by a moderate-to-large effect size (d = 0.72;d = 0.78).Conclusion:Consequently, male smokers exhibit an altered postexercise proinflammatory profile compared with age- and fitness-matched nonsmokers. [ABSTRACT FROM PUBLISHER]

Copyright of Applied Physiology, Nutrition & Metabolism is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The "westernization" of global eating and lifestyle habits is associated with the growing rate of chronic diseases, mainly cardiovascular diseases, cancer, type 2 diabetes mellitus, and respiratory diseases. The primary prevention approach is to make nutritional and behavioral changes, however, there is another important determinant of our health that only recently has been considered and is the presence of beneficial microorganisms and their products in our gastrointestinal tract. Microorganisms living in our body can alter the fate of food, drugs, hormones, and xenobiotics, and recent studies point to the use of microorganisms that can counteract the harmful effects of certain compounds introduced or produced endogenously in our body. This review considers the effects of the western lifestyle on adiposity, glucose metabolism, oxidative markers and inflammation profile, emphasizes on the studies that have investigated bacterial strains and products of their metabolism that are beneficial under this lifestyle, and examines the screening strategies that recent studies are using to select the most promising probiotic isolates. In addition, we consider the relevance of studying the microbiota of metabolically healthy people under a western lifestyle for the understanding of the key components that delay the development of chronic diseases. [ABSTRACT FROM AUTHOR]

Bronchial asthma is a chronic inflammatory disease of the airways that is characterized by episodes of shortness of breath, expiratory dyspnea, cough, wheezing, and pulmonary emphysema. At the present time, asthma is a global public health problem and affects about 5% of the worldwide population. Although a wide range of anti-inflammatory drugs is available, uncontrolled or poorly controlled asthma is still a problem, requiring the development of novel therapeutic approaches. Intense studies of the molecular mechanisms of asthma in transgenic animals performed since the 1990s implicated cytokines, such as IL-4, IL-5, and IL-13, and their receptors in the initiation and maintenance of asthma. These findings led to anticytokine therapy as a novel approach for bronchial asthma treatment. To date, many preclinical and clinical studies have been performed in this field especially with drugs based on humanized monoclonal antibodies, soluble receptors, peptide inhibitors, etc. The review summarizes the data from preclinical and clinical studies of anti-cytokine therapeutics in humans. [ABSTRACT FROM AUTHOR]

Copyright of Internal Medicine / Medicină Internă is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Airway epithelium is the first line of defense against exposure of the airway and lung to various inflammatory stimuli. Ciliary beating of airway epithelial cells constitutes an important part of the mucociliary transport apparatus. To be effective in transporting secretions out of the lung, the mucociliary transport apparatus must exhibit a cohesive beating of all ciliated epithelial cells that line the upper and lower respiratory tract. Cilia function can be modulated by exposures to endogenous and exogenous factors and by the viscosity of the mucus lining the epithelium. Cilia function is impaired in lung diseases such as COPD and asthma, and pharmacologic agents can modulate cilia function and mucus viscosity. Cilia beating is reduced in COPD, however, more research is needed to determine the structural-functional regulation of ciliary beating via all signaling pathways and how this might relate to the initiation or progression of obstructive lung diseases. Additionally, genotypes and how these can influence phenotypes and epithelial cell cilia function and structure should be taken into consideration in future investigations. [ABSTRACT FROM AUTHOR]

Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1β (IL-1β) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3 × per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice. [ABSTRACT FROM AUTHOR]

Drug classes used in the treatment of Chronic Obstructive Pulmonary Disease (COPD) have not changed for many years, and none to date have shown disease-modifying activity. Statins are used to help reduce cardiovascular risk, which is high in many patients with COPD. Their use has been associated with improvements in some respiratory manifestations of disease and reduction in all-cause mortality, with greatest reductions seen in patients with the highest inflammatory burden. The mechanism for these effects is poorly understood. Neutrophils are key effector cells in COPD, and correlate with disease severity and inflammation. Recent in vitro studies have shown neutrophil functions are dysregulated in COPD and this is thought to contribute both to the destruction of lung parenchyma and to the poor responses seen in infective exacerbations. In this article, we will discuss the potential utility of statins in COPD, with a particular emphasis on their immune-modulatory effects as well as presenting new data regarding the effects of statins on neutrophil function in vitro. [ABSTRACT FROM AUTHOR]