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[Display omitted] • Zinc oxide nanoparticles were able to cause pulmonary dysfunction in Wistar rats. • Bryophyllum pinnatum increased antioxidant activities and upregulated the expression of antioxidant genes. • Bryophyllum pinnatum downregulated the expression of pro-inflammatory genes in zinc oxide nanoparticles-induced rats. • Bryophyllum pinnatum could reverse dysfunctional autophagy in rats' lungs as induced by zinc oxide nanoparticles. Lung inflammation as a result of exposure to toxicants is a major pathological problem. Autophagy (AP) is a process of cell self-digestion and can be disrupted by environmental toxicants, leading to oxidative stress, inflammation and cellular damage. Bryophyllum pinnatum (Lam.) Oken has been used in folklore medicine to manage pathological abnormalities, including inflammation, but mechanisms remain unclear. This work investigated the effects of Bryophyllum pinnatum ethanol leaf extract (BP) on dysfunctional AP in the lungs of Wistar rats exposed to zinc oxide nanoparticles (ZONPs). The experimental rats were orally administered ZONPs for seven days (10 mg/kg). Some exposed rats were post-treated with BP (62.5 and 125 mg/kg) through oral gavage. Oxidative stress, inflammation, and apoptotic and autophagic parameters were assessed using biochemical assay and gene expression methods. Several indices of pulmonary damage were also evaluated. PCR analysis suggested that ZONP downregulated the expression of pro-autophagy-related genes (Beclin 2, ATG5, DAPK, and FOXP3) and upregulated the expression of the TNF-alpha, NF-Kb, LC3 and Bcl2 genes. In contrast, BP significantly (p < 0.0001) reversed ZONP-induced pulmonary toxicity and oxidative stress. It reduced MDA levels and increased SOD, CAT, GSH and GPxD activities. BP significantly (p < 0.0001) downregulated the expressions of proinflammatory genes (IL-6 and JNK) and upregulated the expressions of IL-10, CAT and SOD genes in ZONP-exposed rats. BP restored the lung's histoarchitectural structure after ZNOP-induced distortion. The results suggested that BP has antioxidant and anti-inflammatory properties, and could effectively restore ZNOP-induced dysfunctional AP in the lungs of Wistar rats. [ABSTRACT FROM AUTHOR]

• Exportin XPO6 was upregulated in COPD pulmonary monocytes. • XPO6 promoted TLR2 expression in monocytes. • XPO6 enhanced MyD88/NF-κB inflammatory signaling via TLR2. • XPO6 facilitated TLR2 mRNA nuclear export in monocytes. Chronic obstructive pulmonary disease (COPD) poses a significant health threat characterized by lung inflammation primarily triggered by pulmonary monocytes. Despite the centrality of inflammation in COPD, the regulatory mechanisms governing this response remain elusive, presenting a challenge for anti-inflammatory interventions. In this study, we assessed the expression of exportins in COPD mouse models, revealing a notable upregulation of XPO6 in the mouse lung (P = 0.0011). Intriguingly, we observed a consistent upregulation of XPO6 in pulmonary monocytes from both human and mouse COPD subjects (P < 0.0001). Furthermore, in human lung tissue, XPO6 expression exhibited a positive correlation with TLR2 expression (P = 0). In vitro investigations demonstrated that XPO6 enhances TLR2 expression, activating the MyD88/NF-κB inflammatory signaling pathway. This activation, in turn, promotes the secretion of pro-inflammatory cytokines such as TNFα, IL-6, and IL-1β in monocytes. Mechanistically, XPO6 facilitates the nuclear export of TLR2 mRNA, ensuring its stability and subsequent protein expression in monocytes. In conclusion, our findings unveil that the upregulation of XPO6 in COPD pulmonary monocytes activates the MyD88/NF-κB inflammatory signaling pathway by facilitating the nuclear export of TLR2 mRNA, thereby identifying XPO6 as a promising therapeutic target for anti-inflammatory interventions in COPD. [ABSTRACT FROM AUTHOR]

• AIM2 is involved in lung chronic inflammation after cigarette smoke exposure. • The activation of AIM2 induces the recruitment to the lung of immunosuppressive cells after cigarette smoke exposure. • The activation of AIM2 induces the release of immunosuppressive cytokines, i.e. IL-10 and TGFβ. • AIM2-induced lung inflammation after cigarette smoke exposure is caspase-1-independent in mice. • STING pathway does not affect AIM2-induced lung inflammation in mice exposed to cigarette smoke. Cigarette smoke is widely known as contributing to chronic inflammation underlying several airway diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. In our previous studies we found that the lung of both COPD and cancer patients were characterized by the presence and activation of the AIM2 inflammasome. Here, we wanted to investigate the upstream step during the establishment of chronic lung inflammation after cigarette smoke exposure. We took advantage of a mouse model of smoking exposure and public scRNAseq data. We found that AIM2 mRNA was expressed in both alveolar type II, B cells, T regulatory (Treg) and macrophages detected in the lung of non-smokers (n = 4) and smokers (n = 3). The activation of AIM2 in smoking mice by using PolydA:dT did not alter cigarette-smoke-induced alveoli enlargement and mucus production, rather it induced higher recruitment of immunosuppressive cells, such as non-active dendritic cells (DCs), Arginase I+ macrophages, myeloid-derived suppressor cells (MDSC) and Tregs. In addition, the inflammatory environment after AIM2 activation in smoking mice was characterized by higher levels of IL-1α, IL-1β, IL-33, TNFα, LDH, IL-10 and TGFβ. This scenario was not altered after the pharmacological inhibition of both caspase-1 and STING pathway. In conclusion, these data suggest that chronic inflammation after cigarette smoke exposure is associated with AIM2 activation, which could lead towards cigarette smoke-associated lung diseases. [ABSTRACT FROM AUTHOR]

• We found that IL-41 pre-treatment alleviated pulmonary inflammatory infiltration, and lung tissue lesions. • IL-41 pre-treatment also limited CS-induced weight loss, and resulted in lower numbers of macrophages in the bronchoalveolar lavage fluid (BALF) and lower percentages of neutrophils and monocytes in the blood. • Furthermore, it promoted the polarization of M2 macrophages rather than M1 macrophages, as determined by immunohistochemistry. • Consistent with its effects on M2 polarization, pre-treatment with IL-41 was associated with higher levels of IL-10 in the bronchoalveolar lavage fluid and lung tissues of CS-exposed animals and lower production of tumor necrosis factor-α(TNF-α), IL-1β and IL-6 in the serum and lung tissues. • These findings suggest that IL-41 could be used therapeutically to treat CS-induced lung inflammatory disorders as it inhibits CS-induced pulmonary inflammation when administered in vivo in mice. Chronic obstructive pulmonary disease (COPD) and other inflammatory lung illnesses are markedly exacerbated by cigarette smoke (CS). The novel cytokine interleukin (IL)-41 has immunoregulatory effects, but data on its function in lung inflammation caused by CS are limited and inconclusive. Our study aimed to investigate the ability of IL-41 to protect against CS-induced lung inflammation in vivo. In this model, mice were exposed to six cigarettes three times daily for 1 h, with 4-hour intervals between exposures, for 5 consecutive days. Mice received an intraperitoneal dose of IL-41 or a negative control 1 day prior to their initial exposure to CS. On day 6, mice were sacrificed to assess the impact of IL-41 on CS-induced lung inflammation. We found that IL-41 pre-treatment alleviated pulmonary inflammatory infiltration and lung tissue lesions. IL-41 pre-treatment also limited CS-induced weight loss, and resulted in lower numbers of macrophages in the bronchoalveolar lavage fluid and lower percentages of neutrophils and monocytes in the blood. Furthermore, it promoted the polarization of M2 macrophages rather than M1 macrophages, as determined by immunohistochemistry. Consistent with its effects on M2 polarization, pre-treatment with IL-41 was associated with higher levels of IL-10 in the bronchoalveolar lavage fluid and lung tissues of CS-exposed animals and lower production of tumor necrosis factor-α, IL-6 and IL-1β in the serum and lung tissues. These findings suggest that IL-41 could be used therapeutically to treat CS-induced lung inflammatory disorders as it inhibits CS-induced pulmonary inflammation when administered in vivo in mice. [ABSTRACT FROM AUTHOR]

Abstract Cigarette smoke (CS) is a major factor that leads to lung inflammation. The prevalence of CS-induced lung injury has continuously increased worldwide. Morin exists in a large member of plants and fruits that has been reported to have antioxidant and anti-inflammatory properties. In the present study, we tested the mechanism and protective effects of morin on CS-induced lung inflammation in mice. The mice were exposed to CS for 2 h twice a day for 4 weeks. Morin (10, 20, and 40 mg/kg) was treated to mice through oral gavage 1 h before CS administration. 24 h after the last CS exposure, the mice were euthanized. The lung tissues were collected and the pathological changes, wet/dry ratio, MPO activity, MDA levels, and P13K/ATK/NF-κB signaling pathway expression were detected. The bronchial alveolar lavage fluid (BALF) was obtained and the levels of inflammatory cells and inflammatory cytokines were measured. The results showed that morin treatment significantly inhibited lung pathological changes, wet/dry ratio, MPO activity, and MDA level. The levels of total cells, neutrophils, macrophages, as well as the production of inflammatory cytokines in the BALF induced by CS were also suppressed by morin. Further research showed that morin dramatically suppressed the activation of P13K/ATK/NF-κB singling pathway induced by CS. This study highlights the protective effects of morin on CS-induced lung inflammation, which may, at least part, be mediated through inhibiting P13K/ATK/NF-κB signaling pathway. These finding demonstrated that morin could be a potential drug for CS-induced lung injury. Highlights • Morin inhibited the pathological changes, wet/dry ratio, MPO activity, and MDA levels of lung tissues. • Morin suppressed the levels of total cells, neutrophils, macrophages, as well as the production of inflammatory cytokines. • Morin dramatically suppressed the activation of P13K/ATK/NF-κB singling pathway induced by CS. [ABSTRACT FROM AUTHOR]

The alveolar surfactant, which composition consists of a unique and complex mixture of lipids and proteins, has immunomodulatory action. This study aimed to evaluate the effects of exogenous surfactant on pulmonary inflammatory response in mice exposed to cigarette smoke (CS). Twenty-four mice C57BL/6 were divided into four groups: control group exposed to ambient air (CG); surfactant treated group (SG); CS exposed group (CSG) and CS exposed group treated with surfactant (CSSG). For five days, CSG and CSSG were exposed to 12 commercial cigarettes/day and SG and CSSG received the surfactant by intranasal instillation. At the end of the experiment, the animals were euthanatized for the collection of bronchoalveolar lavage fluid (BALF) and lungs. The total number of leukocytes in BALF increased in CSG compared to CG, however, there was a decrease in CSSG compared to CSG. There was an increase in lipid peroxidation in SG and CSG compared to CG while there was a decrease in CSSG compared to CSG. Regarding the antioxidant enzymes, the catalase (CAT) activity increased in all groups compared to CG and the superoxide dismutase (SOD) activity decreased in CSG compared to the CG and SG. There was an increase in TNF in SG, CSG and CSSG compared to CG. There was an increase in IL-17 in CSSG compared to CG. There was an increase in CCL5 in SG and CSSG compared to CG. Therefore, our results demonstrated that the administration of exogenous surfactant was able to decrease the oxidative processes in the lungs of mice induced by short-term exposure to CS. [ABSTRACT FROM AUTHOR]

Schisandrin B (SchB), a dibenzocyclooctadiene derivative isolated from Schisandra chinensis , has been reported to have anti-inflammatory effects. However, the protective effects of SchB on cigarette smoke (CS)-induced lung inflammation remain unclear. This study was to investigate the effects of SchB on CS-induced lung inflammation in mice. The mice were exposed to CS to develop lung inflammation. SchB was given 1 h before CS exposure daily for five consecutive days. The levels of inflammatory mediators TNF-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid (BALF) were measured in this study. SOD, GSH, MPO and MDA contents were also detected. Furthermore, the expression of Nrf-2 and NF-κB were detected by western blot analysis. Histopathological analyses showed that SchB had protective effects against CS-induced lung inflammation. The levels of inflammatory mediators TNF-α, IL-1β, and IL-6 in BALF were also inhibited by SchB. CS-induced MPO activity and MDA content were inhibited by SchB. The levels of SOD and GSH were up-regulated by SchB. SchB significantly inhibited CS-induced NF-κB activation and up-regulated the expression of Nrf2 and HO-1. In conclusion, these data suggest that SchB protects against CS-induced lung inflammation by activating Nrf2 and inhibiting NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Cigarette smoke is the one of the major factors that leads to chronic obstructive pulmonary disease (COPD). Inflammation and oxidant stress have been known to play critical roles in the development of COPD. Platycodin D (PLD) has been reported to have anti-inflammatory and anti-oxidant effects. In this study, we aimed to investigate the protective effects of PLD on cigarette smoke (CS)-induced lung inflammation in mice. PLD was adminstrated i.p. to mice 2 h before CS exposure daily for five consecutive days. The production of inflammatory cytokines TNF-α and IL-1β were measured by ELISA. The levels of malonaldehyde (MDA) and nitric oxide (NO) were also detected in this study. The expression of nuclear factor-erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NF-κB, and IκBα were detected by western blot analysis. The results showed that PLD significantly attenuated CS-induced lung pathological changes, inflammatory cells infiltration, as well as TNF-α and IL-1β production. CS-induced MDA and NO production were also inhibited by treatment of PLD. Western blot analysis showed that PLD significantly suppressed CS-induced NF-κB activation. In addition, PLD was found to increase the expression of Nrf2 and HO-1. Taken together, these results indicated that PLD protected against CS-induced lung inflammation by inhibiting inflammatory and oxidative response through activating Nrf2 signaling pathway. PLD might be an effective treatment for CS-induced lung inflammation. [ABSTRACT FROM AUTHOR]

• ARDS activates the tumor microenvironment and enhances lung metastasis. • BRD4 plays a vital role in inflammation-mediated tumor metastasis. • BRD4 is involved in lung inflammation-mediated tumor metastasis by up regulating the p65 and STAT3 expression. • LPS stimulated the expression of TLR4 and BRD4 in both in vitro and in vivo assays. • Targeting BRD4 could be beneficial in lung inflammation and lung tumor metastasis. Acute respiratory distress syndrome (ARDS) is associated with severe lung inflammation, edema, hypoxia, and high vascular permeability. The COVID-19-associated pandemic ARDS caused by SARS-CoV-2 has created dire global conditions and has been highly contagious. Chronic inflammatory disease enhances cancer cell proliferation, progression, and invasion. We investigated how acute lung inflammation activates the tumor microenvironment and enhances lung metastasis in LPS induced in vitro and in vivo models. Respiratory illness is mainly caused by cytokine storm, which further influences oxidative and nitrosative stress. The LPS-induced inflammatory cytokines made the conditions suitable for the tumor microenvironment in the lungs. In the present study, we observed that LPS induced the cytokine storm and promoted lung inflammation via BRD4, which further caused the nuclear translocation of p65 NF-κB and STAT3. The transcriptional activation additionally triggers the tumor microenvironment and lung metastasis. Thus, BRD4-regulated p65 and STAT3 transcriptional activity in ARDS enhances lung tumor metastasis. Moreover, LPS-induced ARDS might promote the tumor microenvironment and increase cancer metastasis into the lungs. Collectively, BRD4 plays a vital role in inflammation-mediated tumor metastasis and is found to be a diagnostic and molecular target in inflammation-associated cancers. [ABSTRACT FROM AUTHOR]

• Aortic ischemia and reperfusion leads to lung inflammatory activation with edema and leukocyte infiltration. • E2 preventive effects include decreasing of edema, iNOS expression and preventing leukocyte infiltration. • E2 is able to prevent the increased expression of ET-1. • Our study can be considered is one more step towards using E2 to prevent the local and remote inflammatory response after descending thoracic aorta cross-clamping. As a consequence of systemic inflammation caused by ischemia and reperfusion (I/R) due to aortic occlusion, the lungs can exhibit increased microvascular permeability, local release of pro-inflammatory mediators, and leukocyte infiltration. Lung tissue infiltration by activated neutrophils is followed by acute respiratory distress syndrome, which is linked to acute pulmonary microvascular damage, high mortality rates, and organ dysfunction. Previous studies have demonstrated that female sex hormones modulate the inflammatory response and that prophylactic treatment with 17β-estradiol (E2) can prevent fatalities and preserve mesenteric perfusion and intestinal integrity after ischemia/reperfusion induced by aortic occlusion. In this study, we focused on the protective effects of estradiol after aortic ischemia/reperfusion by evaluating lung injury and endothelial alterations. Upon anesthesia and mechanical ventilation, male rats were subjected to aortic occlusion for 20 min, followed by 2 h of reperfusion. In parallel, one group of rats received a single injection of estradiol (280 µg/kg, i.v.) 30 min before ischemia. We observed increased serum concentrations of IL-1β, IL-6 and IL-10 in the I/R rats and E2 was able to reduce them. E2 effects after 2 h of reperfusion resulted mainly in decreasing of edema, iNOS expression and preventing leukocyte infiltration. Overall, our data indicate that estradiol might be a supplementary approach to deal with systemic processes and lung deterioration. [ABSTRACT FROM AUTHOR]

The antler of Sika deer ( Cervus nippon Temminck) has been used a natural medicine in Korea, China and Japan, and a monoacetyldiaglyceride (1-palmitoyl-2-linoleoyl-3-acetylglycerol, PLAG) was found in the antler of Sika deer as a constituent for immunomodulation. In this study, we investigated protective effects of EC-18 (a synthetic copy of PLAG) on inflammatory responses using a cigarette smoke with lipopolysaccharide (LPS)-induced airway inflammation model. Mice were exposed to cigarette smoke for 1 h per day for 3 days. Ten micrograms of LPS dissolved in 50 μL of PBS was administered intra nasally 1 h after the final cigarette smoke exposure. EC-18 was administered by oral gavage at doses of 30 and 60 mg/kg for 3 days. EC-18 significantly reduced the number of neutrophils, reactive oxygen species production, cytokines and elastase activity in bronchoalveolar lavage fluid (BALF) compared with the cigarette smoke and LPS induced mice. Histologically, EC-18 attenuated airway inflammation with a reduction in myeloperoxidase expression in lung tissue. Additionally, EC-18 inhibited the phosphorylation of NF-κB and IκB induced by cigarette smoke and LPS exposure. Our results show that EC-18 effectively suppresses neutrophilic inflammation induced by cigarette smoke and LPS exposure. In conclusion, this study suggests that EC-18 has therapeutic potential for the treatment of chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Linalool, a natural compound that exists in the essential oils of several aromatic plants species, has been reported to have anti-inflammatory effects. However, the effects of linalool on cigarette smoke (CS)-induced acute lung inflammation have not been reported. In the present study, we investigated the protective effects of linalool on CS-induced acute lung inflammation in mice. Linalool was given i.p. to mice 2 h before CS exposure daily for five consecutive days. The numbers of macrophages and neutrophils in bronchoalveolar lavage fluid (BALF) were measured. The production of TNF-α, IL-6, IL-1β, IL-8 and MCP-1 were detected by ELISA. The expression of NF-κB was detected by Western blotting. Our results showed that treatment of linalool significantly attenuated CS-induced lung inflammation, coupled with inhibited the infiltration of inflammatory cells and TNF-α, IL-6, IL-1β, IL-8 and MCP-1 production. Meanwhile, treatment of linalool inhibited CS-induced lung MPO activity and pathological changes. Furthermore, linalool suppressed CS-induced NF-κB activation in a dose-dependent manner. In conclusion, our results demonstrated that linalool protected against CS-induced lung inflammation through inhibiting CS-induced NF-κB activation. [ABSTRACT FROM AUTHOR]

Cigarette smoke has been reported to be the major cause of chronic obstructive pulmonary disease (COPD). It causes persistent inflammation by regulating the redox-sensitive pathways. Forsythiaside, an active constituent isolated from the Chinese medicinal herb Forsythia suspensa , has been reported to have anti-inflammatory and anti-oxidant effects. Thus, in this study, we investigated the protective effects of forsythiaside against cigarette smoke-induced lung inflammation in mice. COPD mice model was established by cigarette smoke. Forsythiaside was given 2 h before cigarette smoke exposure for five consecutive days. Bronchoalveolar lavage fluid and lung tissues were collected to assess pathological changes, lipid peroxidation, inflammatory cytokine production, Nrf-2, and NF-κB expression. Our results showed that forsythiaside attenuated the infiltration of inflammatory cells, NO and inflammatory cytokines TNF-α, IL-6 and IL-1β production, and reversed the CS-induced decrease of glutathione/glutathione disulfide (GSH/GSSG) ratio. Western blot analysis showed that forsythiaside inhibited cigarette smoke-induced NF-κB activation. In addition, forsythiaside dose-dependently up-regulated the expression of Nrf2 and HO-1. In conclusion, forsythiaside protected against cigarette smoke-induced lung injury through activating Nrf2 and inhibiting NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Pasteurellosis caused by Pasteurella multocida manifest often as respiratory infection in farmed small ruminants. Although the incidence of pasteurellosis due to P. multocida mainly takes the form of pneumonia, there is limited information on host factors that play a role in disease pathogenesis in the milieu of host-pathogen interactions. Nuclear factor-erythroid 2 related factor 2 (Nrf-2), a critical regulator for various inflammatory and immune responses by controlling oxidative stress, may play an important role in the processes of inflammation induced by P. multocida. In this study, linalool, a natural compound of the essential oils in several aromatic plant species, elevated nuclear Nrf-2 protein translocation in the A549 lung cell line and in vivo. The P. multocida-induced pro-inflammatory cytokines expression was abrogated by Nrf-2 siRNA. Postponed treatment with linalool decreased lung neutrophil accumulation and enhanced clearance of P. multocida. Furthermore, linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6. In addition, animals treated with linalool had a marked improvement in survival. These findings have uncovered that linalool acts as a novel Nrf-2 activator for a novel therapeutic strategy in pathogen-mediated lung inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Inflammation and oxidative stress are associated with airway diseases. There is growing evidence that Atorvastatin could be used as a therapy for these conditions. Objective: On these bases, we evaluated Atorvastatin as a protective and reversal treatment for the allergic airway diseases in mice model. We also looked at the possible interaction with the currently used effective medication. Methods: Mice were sensitized and challenged with ovalbumin (OVA) to develop features of allergic airway diseases mainly of bronchial inflammation. Atorvastatin was injected during or after the sensitization and challenge process to evaluate its protective or reversal effects, respectively. Total and differential cells in the BAL fluids together with IL-4, IL-5 and IL-10 cytokine levels were evaluated. Total IgE and cholesterol levels in serum were studied. Results: In the protective phase, Atorvastatin inhibited the OVA-induced cellular infiltration of lung bronchi, decreased IL-4 and IL-5 and prevented the increase in IL-10 cytokine levels. Also, it reduced the OVA-induced high serum total IgE level. Injection of Atorvastatin after challenge was not effective in reversing the inflammatory process, with no major contribution towards augmenting the actions of Dexamethasone. The cholesterol lowering effect was marked in the protective phase while less effective for the reversal phase. Conclusion: Our results indicate that Atorvastatin reduced the allergic inflammatory features in mice and it could be useful towards developing a better therapeutic regimen for the treatment of allergic diseases. [Copyright &y& Elsevier]

Abstract: Allergic asthma is a chronic inflammatory condition of the lung characterized by reversible airway obstruction, high serum immunoglobulin (Ig) E levels, and chronic airway inflammation. A number of cells including mast cells, T cells, macrophages and dendritic cells play a role in the pathogenesis of the disease. Janus kinase (JAK)-3, a non-receptor protein tyrosine kinase, traditionally known to mediate cytokine signaling, also regulates functional responses of these cells. In this review the role of JAK-3 in regulating various pathogenic processes in allergic asthma is discussed. We propose that targeting JAK-3 is a rationale approach to control the inflammatory responses of multiple cell types responsible for the pathogenesis of allergic asthma. [Copyright &y& Elsevier]

Abstract: Gram-positive Staphylococcus aureus releases classical enterotoxins which aggravates allergic airway diseases. However, little is known about the mechanisms underlying the cell influx exacerbation in asthmatic individuals under exposure to Staphylococcal enterotoxins. We therefore aimed to investigate the effects of airways exposure to Staphylococcal enterotoxin A (SEA) to pulmonary leukocyte recruitment in rats sensitized and challenged with ovalbumin (OVA). Rats were exposed to SEA at 4h prior to OVA challenge or at 4h post-OVA challenge. Bronchoalveolar lavage (BAL) fluid, bone marrow and lung tissue were obtained at 24h after OVA challenge. Pre-exposure to SEA markedly enhanced the eosinophil counts in both BAL fluid and pulmonary tissue in OVA-challenged rats, whereas neutrophil and mononuclear cell counts remained unchanged. In bone marrow, pre-exposure to SEA alone significantly increased the number of eosinophils, and that was further increased in OVA-challenged rats. Exposure to SEA post-OVA challenge did not affect the number of eosinophils, neutrophils and mononuclear cells in BAL fluid. Pre-exposure to the endotoxin lipopolyssacharide (LPS) in OVA-challenged animals rather enhanced the neutrophil number in BAL fluid. In rats pre-exposed to SEA and OVA-challenged, a marked elevation in the levels of TNF-α and eotaxin (but not of IL-10) in BAL fluid was observed. The eotaxin levels increased by about of 3-fold in alveolar macrophages treated with SEA in vitro. In conclusion, airways pre-exposure to SEA causes a selective increase in eosinophil number in BAL fluid and bone marrow of OVA-challenged rats by mechanisms involving enhancement of TNF-α and eotaxin synthesis. [Copyright &y& Elsevier]

Abstract: Asthma is a chronic respiratory disease, the incidence of which is increasing globally. The existing therapy is inadequate and has many adverse effects. It needs a better therapeutic molecule preferably of natural origin, which has negligible or no adverse effects. In view of this, we evaluated Glycyrrhizin (GRZ), a major constituent of a plant Glycyrrhiza glabra, for its efficacy on asthmatic features in a mouse model of asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to develop the asthmatic features such as airway hyperresponsiveness: allergen induced airway constriction and airway hyperreactivity (AHR) to methacholine (MCh), and pulmonary inflammation. The mice were orally treated with GRZ (2.5, 5, 10 and 20 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect, respectively on the above asthmatic features. The status of airway hyperresponsiveness was measured by monitoring specific airway conductance (SGaw) using a non-invasive method and the pulmonary inflammation was assessed by haematoxylin and eosin staining of lung sections. Several other parameters associated with asthma such as interleukin (IL)-4, IL-5 interferon-γ (IFN-γ), OVA-specific IgE, total IgG2a and cortisol were measured by ELISA. GRZ (5 mg/kg) markedly inhibited OVA-induced immediate airway constriction, AHR to MCh (p <0.01), lung inflammation, and infiltration of eosinophils in the peribronchial and perivascular areas. It prevented the reduction of IFN-γ (p <0.02), and decreased IL-4 (p <0.05), IL-5 (p <0.05) and eosinophils (p <0.0002) in the BAL fluid. Also, it reduced OVA-specific IgE levels (p <0.01) and prevented the reduction of total IgG2a (p <0.01) in serum. We have also showed that it has no effect on serum cortisol levels. Our results demonstrate that GRZ alleviates asthmatic features in mice and it could be useful towards developing a better therapeutic molecule in the future. [Copyright &y& Elsevier]

Abstract: Thymoquinone (TQ), the main active constituent of the volatile oil extracted from Nigella sativa''s seeds, has been reported to have an anti-inflammatory and immune stimulatory effect on bronchial asthma and inflammation. However, little is known about the factors and mechanisms underlying these effects. In the present study, we examined the effect of TQ on airway inflammation in a mouse model of allergic asthma. Intraperitoneal injection of TQ before airway challenge of ovalbumin (OVA)-sensitized mice resulted in a marked decrease in lung eosinophilia and the elevated Th2 cytokines observed after airway challenge with OVA antigen; both in vivo, in the bronchoalveolar lavage (BAL) fluid and in vitro, following stimulation of lung cells with OVA. TQ also decreased the elevated serum levels of OVA-specific IgE and IgG1. Histological examination of lung tissue demonstrated that TQ significantly inhibited allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells. While TQ showed a significant effect in inhibiting IL-4, IL-5 and IL-13 and some effect in inducing IFN-γ production in the BAL fluid, it did show a slight effect on in vitro production of IL-4 by cultured lung cells stimulated with OVA antigen. These data suggest that TQ attenuates allergic airway inflammation by inhibiting Th2 cytokines and eosinophil infiltration into the airways; thus demonstrating its potential anti-inflammatory role during the allergic response in the lung. [Copyright &y& Elsevier]

• Pinocembrin could relieve LPS and BLM induced lung inflammation. • Pinocembrin attenuated lung inflammation via inhibiting TLR4-NF-κB-NLRP3 pathway. • Pinocembrin may be a candidate compound for anti-lung inflammation drug development. Inflammation is a defense response of the body to stimuli. Lung injury caused by external stimuli can stimulate inflammatory cells to accumulate at the site of injury and secrete cytokines. Pinocembrin is a flavonoid with anti-inflammatory effects. Based on previous studies, we further explored the anti-inflammatory mechanisms of pinocembrin in vitro and in vivo. In vitro studies indicated that pinocembrin inhibited lipopolysaccharide (LPS)-stimulated inflammatory response in macrophages. In vivo studies also showed that pinocembrin could reduce LPS and bleomycin (BLM) induced lung inflammatory response in mice. Further mechanistic studies indicated that pinocembrin could regulate the TLR4-NF-κB signaling pathway and suppressed the activation and assembly of NLRP3 inflammasomes. In summary, pinocembrin could relieve pulmonary inflammatory response induced by LPS and BLM mainly via inhibiting TLR4-NF-κB-NLRP3 inflammasome axis. These results contribute to the understanding of the anti-inflammatory mechanisms of pinocembrin and serve as reference for future research on pinocembrin. [ABSTRACT FROM AUTHOR]

Abstract: Background and objective: Low-level laser therapy (LLLT) is a known modulator of inflammatory process. Herein we studied the effect of 660 nm diode laser on mRNA levels of neutrophils anti-apoptotic factors in lipopolysaccharide (LPS)-induced lung inflammation. Study design/methodology: Mice were divided into 8 groups (n =7 for each group) and irradiated with energy dosage of 7.5 J/cm2. The Bcl-xL and A1 mRNA levels in neutrophils were evaluated by Real Time-PCR (RT-PCR). The animals were irradiated after exposure time of LPS. Results: LLLT and an inhibitor of NF-κB nuclear translocation (BMS 205820) attenuated the mRNA levels of Bcl-xL and A1 mRNA in lung neutrophils obtained from mice subjected to LPS-induced inflammation. Conclusion: LLLT reduced the levels of anti-apoptotic factors in LPS inflamed mice lung neutrophils by an action mechanism in which the NF-κB seems to be involved. [Copyright &y& Elsevier]

• Airways exposure to SEB causes acute lung inflammation. • Airways exposure to SEB induces accumulation of bone marrow (BM) immature neutrophils. • SEB airways exposure increases BM neutrophils adhesion to ICAM-1. • SEB airways exposure did not modify BM neutrophils MAC-1 and LF1A-α expression. • SEB induces BM elevations of GM-CSF, G-CSF, IFN-γ, TNF-α, KC/CXCL1, SDF-1α and MIP-2. • Our results contribute to elucidate BM events during SEB-induced lung inflammation. The lung infections by Staphylococcus aureus are strongly associated with its ability to produce enterotoxins. However, little is known about the mechanisms underlying trafficking of bone marrow (BM) neutrophils during airway inflammation induced by Staphylococcal enterotoxin B (SEB). We therefore aimed to investigate the effects of mouse airways SEB exposure on BM neutrophil counts and its adhesive properties as well as on the release of cytokines/chemokines that orchestrate BM neutrophils trafficking to lung tissue. Male BALB/c mice were intranasally exposed to SEB (1 µg), and at 4, 16 and 24 h thereafter, BM, circulating blood, bronchoalveolar lavage (BAL) fluid and lung tissue were collected. BM neutrophils adhesion, MAC-1 and LFA1-α expressions (by flow cytometry) as well as measurement of cytokine and/or chemokines levels were assayed after SEB-airway exposure. Prior exposure to SEB promoted a marked influx of neutrophils to BAL and lung tissue, which was accompanied by increased counts of BM immature neutrophils and blood neutrophilia. BM neutrophil expressions of LFA1-α and MAC-1 were unchanged by SEB exposure whereas a significant enhancement of adhesion properties to VCAM-1 was observed. The early phase of airway SEB exposure was accompanied by high levels of GM-CSF, G-CSF, IFN-γ, TNF-α and KC/CXCL1, while the latter phase by the equilibrated actions of SDF1-α and MIP-2. Mouse airways exposure to SEB induces BM cytokines/chemokines release and their integrated actions enhance the adhesion of BM neutrophils leading to acute lung injury. [ABSTRACT FROM AUTHOR]

Pasteurellosis caused by Pasteurella multocida manifest often as respiratory infection in farmed small ruminants. Although the incidence of pasteurellosis due to P. multocida mainly takes the form of pneumonia, there is limited information on host factors that play a role in disease pathogenesis in the milieu of host-pathogen interactions. Nuclear factor-erythroid 2 related factor 2 (Nrf-2), a critical regulator for various inflammatory and immune responses by controlling oxidative stress, may play an important role in the processes of inflammation induced by P. multocida. In this study, linalool, a natural compound of the essential oils in several aromatic plant species, elevated nuclear Nrf-2 protein translocation in the A549 lung cell line and in vivo. The P. multocida-induced pro-inflammatory cytokines expression was abrogated by Nrf-2 siRNA. Postponed treatment with linalool decreased lung neutrophil accumulation and enhanced clearance of P. multocida. Furthermore, linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6. In addition, animals treated with linalool had a marked improvement in survival. These findings have uncovered that linalool acts as a novel Nrf-2 activator for a novel therapeutic strategy in pathogen-mediated lung inflammation., (Copyright © 2014 Elsevier B.V. All rights reserved.)