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Introduction: T cells play a critical role in inflammatory diseases. The aim of the present study was to investigate the effects of Majie cataplasm (MJC) on asthma and to propose a possible mechanism involved in this process., Methods: Airway inflammation, infiltration of inflammatory cells, levels of interleukin (IL)-4, IL-10, IL-17, and interferon (IFN)-γ, levels of Th2, Treg, Th17, and Th1 cells, and the expressions of IL-4, IL-10, IL-17, IFN-γ, GATA binding protein 3 (GATA-3), Foxp3, RAR-related orphan receptor gamma (RORγt), and T-bet were detected., Result: MJC treatment reduced lung airway resistance and inflammatory infiltration in lung tissues. MJC treatment also reduced the numbers of eosinophils and neutrophils in the blood and bronchoalveolar lavage fluid (BALF). The levels of IL-4 and IL-17 in the blood, BALF, and lungs were suppressed by MJC, and IFN-γ and IL-10 were increased. Furthermore, MJC suppressed the percentage of Th2 and Th17 and increased the percentage of Th1 and Treg in spleen cells. In addition, MJC can inhibit asthma by increasing expressions of IFN-γ, IL-10, T-bet, and Foxp3, as well as decreasing expressions of IL-4, IL-17, GATA-3, and RORγt., Conclusion: MJC may improve airway hyperresponsiveness and inflammation by regulating Th1/Th2/Treg/Th17 balance in ovalbumin-induced rats. And MJC may be a new source of anti-asthma drugs., (© 2024 S. Karger AG, Basel.)

Background: Houttuynia cordata is an herbal compound that grows in China and exhibits anti-inflammatory, antiviral, and antioxidant properties. Additionally, pyroptosis is mediated by the activated NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome after stimulation by various inflammatory factors in asthma., Objective: To investigate the effect of sodium houttuyfonate on NLRP3 inflammasome-related pyroptosis and Th1/Th2 immune imbalance in asthma., Methods: Asthmatic mice model were made, sodium houttuyfonate was injected intraperitoneally to treat the asthmatic mice. Airway reactivity, cell classification and counting in the bronchoalveolar lavage fluid were measured. Hematoxylin-eosin and periodic acid-Schiff staining were used to analyze airway inflammation and mucus hypersecretion. Beas-2b cells were cultured, LPS, NLRP3 antagonist (Mcc950) and sodium houttuyfonate were used to intervene the Beas-2b cells, NLRP3, ASC, caspase-1, GSDMD, IL-1β, and IL-18 expression in the lung tissue and cells were analyzed using immunohistochemistry and western blot, while qRT- PCR was performed to analyze the mRNA contents in the pulmonary and the cells, respectively. Th1 and Th2 cytokines (IL-4 and IFN-γ) were detected with ELISA and the proportions of Th1 and Th2 in splenocyte were detected by flow cytometry., Results: Airway reactivity decreased in sodium houttuyfonate group when compared with asthmatic group mice. In the BALF, the numbers of leukocytes, eosinophils, neutrophils, lymphocytes, and macrophages were significantly lower in sodium houttuyfonate group mice than in asthmatic group mice. The proportion of TH1/TH2 cells in spleen cells and IFN-γ /IL-4 in plasma increased in sodium houttuyfonate treatment group when compared with asthma group. Immunohistochemistry, western blot and RT-PCR showed that the expressions of NLRP3, ASC, caspase-1, GSDMD, IL-1β and IL-18 were decreased in the lung tissue of mice after treated with sodium houttuyfonate when compared with those in the asthma group. However, sodium houttuyfonate combined with dexamethasone induced a stronger effect on NLRP3-related pyroptosis and Th1/Th2 immune imbalance compared to sodium houttuyfonate or dexamethasone alone. Beas-2b cells were cultured in vitro, sodium houttuyfonate can alleviate LPS-induced ASC, casepase-1, GSDMD, IL-18 and IL-1β increasing, especially in SH (10 μg/ml) treated group, but the effect less than Mcc950., Conclusions: Sodium houttuyfonate can alleviated NLRP3-related pyroptosis and Th1/Th2 immune imbalance to reduce asthma airway inflammation and airway reactivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Bronchial asthma is one of the most chronic pulmonary diseases and major public health problems. In general, asthma prevails in developed countries than developing countries, and its prevalence is increasing in the latter. For instance, the hygiene hypothesis demonstrated that this phenomenon resulted from higher household hygienic standards that decreased the chances of infections, which would subsequently increase the occurrence of allergy. In this review, we attempted to integrate our knowledge with the hygiene hypothesis into beneficial preventive approaches for allergic asthma. Therefore, we highlighted the studies that investigated the correlation between allergic asthma and the two different types of infections that induce the two major antagonizing arms of T cells. This elucidation reflects the association between various types of natural infections and the immune system, which is predicted to support the main objective of the current research on investigating of the benefits of natural infections, regardless their immune pathways for the prevention of allergic asthma. We demonstrated that natural infection with Mycobacterium tuberculosis (Mtb) prevents the development of allergic asthma, thus Bacille Calmette-Guérin (BCG) vaccine is suggested at early age to mediate the same prevention particularly with increasing its efficiency through genetic engineering-based modifications. Likewise, natural helminth infections might inhabit the allergic asthma development. Therefore, helminth-derived proteins at early age are good candidates for designing vaccines for allergic asthma and it requires further investigation. Finally, we recommend imitation of natural infections as a general strategy for preventing allergic asthma that increased dramatically over the past decades., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Abdelaziz, Ji, Wan, Abouelnazar, Abdelwahab and Xu.)

Ginsenoside Rh1 (Rh1) has anti-inflammatory effects in asthma mice, but the underlying mechanism remains unclear. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to construct asthma model. Mice received Rh1 or tiotropium bromide 0.5 h before OVA challenge. Airway morphology and airway remodeling were assessed by HE staining and Masson's trichrome staining, respectively. Th1/Th2 cytokines in serum or broncho alveolar lavage fluid (BALF) were measured by ELISA kits. Rh1 significantly alleviated the lung resistance and airway resistance, and reduced the number of total inflammation cells, eosinophils, neutrophils, and lymphocytes in BALF of the asthmatic mice. The morphological changes and collagen deposition of airway were also reduced by Rh1 in asthmatic mice. The increase of Eotaxin, IL-4, IL-5, IL-13, and IL-33 and the decrease of IL-12 and IFN-γ in both BALF and serum of OVA exposed mice were reversed by Rh1. Rh1 attenuates OVA-induced asthma in the mice model by regulating Th1/Th2 cytokines balance., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Ethnopharmacological Relevance: Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or "Nai-Zi-Lai" in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases. However, the pharmacological mechanisms of HCZP remain unrevealed., Aim of the Study: To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA., Materials and Methods: A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA., Results: Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased., Conclusions: HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action., Methods: In vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4 + T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested., Results: GITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children., Conclusions: This study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4 + T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma.

Paediatric asthma is a common inflammatory disease in children. Atractylenolide III is an active component of the Atractylodes rhizome, an herbal medicine that has been used as an asthma treatment. This study aimed to explore the effects and underlying mechanisms of atractylenolide III in IL-4-induced 16HBE cells and ovalbumin-induced asthmatic mice. The results showed that IL-4 stimulation significantly decreased, and atractylenolide III treatment increased, growth and apoptosis of 16HBE cells. In 16HBE cells, administration of atractylenolide III also significantly suppressed the IL-4-induced increases in the expression of cleaved caspase-1; apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC); and nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3). Moreover, the numbers of total leukocytes, neutrophils, eosinophils, and macrophages significantly increased in ovalbumin-induced mice, and then decreased after atractylenolide III treatment. In ovalbumin-induced asthmatic mice, atractylenolide III treatment also significantly inhibited NLRP3 inflammasome activation and restored the Th1/Th2 balance. These results indicate that atractylenolide III reduced NLRP3 inflammasome activation and regulated the Th1/Th2 balance in IL-4 induced 16HBE cells and ovalbumin-induced asthmatic mice, suggesting it has a protective effect that may be useful in the treatment of paediatric asthma., (© 2020 John Wiley & Sons Australia, Ltd.)

The role of B7-DC in T-cell responses remains controversial because both coinhibitory and costimulatory functions have been reported in various experimental systems in vitro and in vivo. In addition to interacting with the coinhibitory receptor PD-1, B7-DC has also been shown to bind repulsive guidance molecule b (RGMb). The functional consequences of the B7-DC/RGMb interaction, however, remain unclear. More than a decade ago, we reported that replacement of a murine B7-DC mutant lysine with serine (K113S) at positive 113 resulted in a loss of binding capacity to PD-1. Nevertheless, K113S remained costimulatory for T cells in vitro, implicating a dual functionality for B7-DC in T-cell responses. Here we show that recombinant K113S protein interacts with RGMb with a similar affinity to wild-type B7-DC. More importantly, K113S costimulates CD4 + T-cell responses via RGMb and promotes Th1 polarization. RGMb is expressed on the surface of naive mouse T cells, macrophages, neutrophils and dendritic cells. Finally, K113S/RGMb costimulation suppresses Th2-mediated asthma and ameliorates small airway inflammation and lung pathology in an experimental mouse model. Our findings indicate that RGMb is a costimulatory receptor for B7-DC. These findings from the K113S variant provide not only a possible explanation for the B7-DC-triggered contradictory effects on T-cell responses, but also a novel approach to investigate the B7-DC/PD-1/RGMb axis. Recombinant K113S or its derivatives could potentially be developed as an agonist for RGMb to costimulate the Th1 response without triggering PD-1-mediated T-cell inhibition.

The present study is designed to determine whether Huai Qi Huang has immunoregulatory effects on the (helper T (Th)) Th1/Th2 and regulatory T cell (Treg)/Th17 balance in ovalbumin (OVA)-induced asthma model mice. Asthma model mice were constructed by OVA treatment and Huai Qi Huang was administered. The amount of migrated inflammatory cells in the bronchoalveolar lavage fluid (BALF) from the OVA mice was counted. The total IgE in the sera was detected by the IgE ELISA kit. Cell suspensions from the lung were stained with antibodies specific for CD4 and the master transcription factors for Th1 (T-box expressed in T cells (T-bet)), Th2 (GATA-binding protein 3 (Gata-3)), Th17 (retinoic acid related orphan receptor γt (RORγt)), and Treg (forkhead box p3 (Foxp3)). The left lobe of the lung was used to prepare a single-cell suspension for flow cytometry to determine whether Huai Qi Huang influenced CD4 + T-cell subsets. Histological analyses were performed by using Hematoxylin and Eosin staining. The mRNA expression levels of the transcription factors were detected by using qRT-PCR. Huai Qi Huang inhibited infiltration of inflammatory cells into the lung, reduced influx of eosinophils (EOSs), lymphocytes (LYMs), neutrophils (NEUs), and macrophages (MACs) in the BALF, and decreased IgE in the serum in OVA-treated mice. Huai Qi Huang could regulate Th1/Th2 and Treg/Th17 via the re-balance of cytokine profiles and change the mRNA expression levels of the transcription factors, T-bet/Gata-3 and Foxp3/RORγt in OVA-treated mice. Our results showed that Huai Qi Huang could correct the imbalance of Th1/Th2 and Treg/Th17 in OVA-induced asthma model mice, indicating its effects on inhibiting the development and severity of asthma., (© 2017 The Author(s).)

Angelicae Sinensis Radix, with nourishing Yin, promoting blood circulation, and moisturizing dryness functions, is commonly used in clinical medicine. In order to investigate the effects and mechanism of Angelica sinensis(AS) on Th1/Th2 and Th17/Treg in mice with asthma and Yin deficiency syndrome, asthmatic and Yin deficiency syndrome Balb/c mice models were established by injecting and inhaling ovalbumin(OVA) and thyroxin. The models were treated with dexamethasone(DXM), AS extract and AS extract+DXM, respectively. Pathological examination of lung tissues was conducted by HE staining, and ELISA was used to detect the levels of IL-4, IL-17, IFN-γ, TGF-β as well as retinoic acid receptor-related orphan receptor (RORγt). Results showed that AS could significantly improve the situation of inflammation infiltration, increase ratios of IFN-γ/IL-4 and TGF-β/IL-17, decrease the levels of RORγt in lung tissues. The AS+DXM group showed a best treatment effect. The results indicated that AS played a therapeutic role for asthma with Yin deficiency syndrome and improved airway inflammation by inhibiting the expression of RORγt in lung tissues and regulating the balance of Th1/Th2 and Th17/Treg., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail. To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy. In our work, we constructed a pcDNA3.1-sIL-4R-NAP plasmid, named PSN, encoding fusion protein of murine sIL-4R and HP-NAP. PSN significantly inhibited airway inflammation, decreased the serum OVA-specific IgE levels and remodeled the Th1/Th2 balance. Notably, PSN is more effective on anti-asthma therapy comparing with plasmid only expressing sIL-4R.

Many plant species containing flavonoids have been widely used in traditional Chinese medicine. Naringin, a well-known flavanone glycoside of citrus fruits, possesses antioxidant, anti-inflammatory, anti-apoptotic, anti-ulcer, anti-osteoporosis, and anti-carcinogenic properties. The aim of the study was to investigate the anti-asthmatic effects of naringin and the possible mechanisms. Asthma model was established by ovalbumin. A total of 50 mice were randomly assigned to five experimental groups: control, model, and dexamethasone (2 mg/kg, orally) and naringin (5 mg/kg, 10 mg/kg, orally). Airway resistance (Raw) were measured, histological studies were evaluated by the hematoxylin and eosin (HE) staining, OVA-specific serum and BALF IgE levels and Th1/Th2 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th1/Th2 cells was evaluated by flow cytometry (FCM). T-bet and GABA3 in the lung were evaluated by Western blot. Our study demonstrated that naringin inhibited OVA-induced increases in Raw and eosinophil count; OVA-induced effects on interleukin (IL)-4 and INF-gamma levels were blunted with naringin administration. Histological studies demonstrated that naringin substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue. Flow cytometry studies demonstrated that naringin substantially inhibited Th2 cells and enhanced Th1 cells. Naringin substantially inhibited GABA3 and increased T-bet. These findings suggest that naringin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

Paeoniflorin has been demonstrated to exert anti-inflammatory and immunomodulatory effects in the animal study. In this study, we investigated immunoregulatory effects of paeoniflorin on anti-asthmatic effects and underlying mechanisms. Asthma model was established by ovalbumin-induced. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg), and paeoniflorin (10 and 20 mg/kg). Airway resistance (Raw) were measured by the forced oscillation technique; histological studies were evaluated by the hematoxylin and eosin (HE) staining; Th1/Th2 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA); Th1/Th2 cells were evaluated by flow cytometry (FCM); and GATA3 and T-bet were evaluated by Western blot. Our study demonstrated that, compared with model group, paeoniflorin inhibited ovalbumin (OVA)-induced increases in Raw and eosinophil count; interleukin (IL)-4, IgE levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-γ level in bronchoalveolar lavage fluid; histological studies demonstrated that paeoniflorin substantially inhibited OVA-induced eosinophilia in lung tissue and lung tissue compared with model group. Flow cytometry studies demonstrated that paeoniflorin can regulate Th1/Th2 balance. These findings suggest that paeoniflorin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

Aim: The aim of the study was to investigate the effect and mechanism of action of synthetic salidroside in an ovalbumin (OVA)-induced asthma model in mice., Method: BALB/c mice were sensitized with an intraperitoneal injection of ovalbumin (OVA) to induce a mouse model of asthma in paracmasis. The mice were treated with dexamethasone as the positive control. At the end of the study, respiratory reactivity was detected, the numbers of various kinds of white blood cells in the bronchoalveolar lavage fluid (BALF) were counted, and the levels of IL-4 and INF-γ in BALF were determined. Quantitative PCR was used to detect the mRNA contents of IL-4 and INF-γ in lung tissue. Histologic examination was performed to observe inflammatory cellular infiltration., Results: Salidroside treatment virtually eliminated airway hyper-reactivity, markedly reduced the eosinophil percent, obviously reduced the levels of IL-4 and raised INF-γ in the bronchoalveolar lavage fluid (BALF) compared with the sham-treated group. Quantitative PCR on the mRNA content of IL-4 and INF-γ provided confirmation. Lung histologic observations showed that salidroside reduced inflammation and edema. These effects were equivalent to the effects of dexamethasone., Conclusion: Synthetic salidroside exhibits an anti-asthma effect which is related to the regulation of Th1/Th2 balance. This provides a new possibility for treatment of allergic asthma., (Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Astragaloside IV is the chief ingredient of Radix Astragali, which has been used in the Traditional Chinese Medicine as a major component of many polyherbal formulations for the repair and regeneration of injured organ and tissues. We tested the anti-asthmatic effects of AST IV and the possible mechanisms. BALB/c mice that were sensitized and challenged to ovalbumin (OVA) were treated with AST IV (40mg/kg and 20mg/kg) 1h before they were challenged with OVA. Our study demonstrated that AST IV inhibited OVA-induced increases in eosinophil count; interleukin (IL)-4 level were recovered in bronchoalveolar lavage fluid increased IFN-γ and IL-10 levels in bronchoalveolar lavage fluid. Histological studies demonstrated that AST IV substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that AST IV substantially increased CD4(+)CD25(+)Foxp3 T cells (Treg). Furthermore quantitative real-time (qPCR) studies demonstrated that AST IV substantially enhanced Foxp3 mRNA expression in lung tissue. These findings suggest that AST IV may effectively ameliorate the progression of airway inflammation and could be used as a therapy for patients with allergic inflammation., (Copyright © 2014. Published by Elsevier GmbH.)

Aim: Ma Huang Tang (Ephedra decoction, MHT) is a famous classical formula from Shang Han Lun by Zhang Zhongjing in the Han Dynasty. The anti-asthmatic effects of MHT and the possible mechanisms were tested., Method: An asthma model was established by ovalbumin (OVA)-induction in mice. A total of forty-eight mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg·kg(-1)) and MHT (5, 10, and 20 mg·kg(-1)). Airway resistance (Raw) was measured by the forced oscillation technique, histological studies were evaluated by hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th17 cells were evaluated by flow cytometry (FCM)., Results: This study demonstrated that MHT inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4 and IL-17 levels were recovered in bronchoalveolar lavage fluid, increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that MHT substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that MHT substantially inhibited Th17 cells., Conclusion: These findings suggest that MHT may effectively ameliorate the progression of asthma, and could be further investigated for potential use as a therapy for patients with allergic asthma., (Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The aim of the study was to investigate the anti-asthmatic effects of baicalin (BA) and the possible mechanisms. Asthma model was established by ovalbumin (OVA) intraperitoneal injection. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and BA (10 mg/kg, 20 mg/kg, 40 mg/kg). Airway resistance (RI) and lung compliance (Cdyn) were measured, histological studies were evaluated by the hematoxylin and eosin staining, Th1/Th2, OVA-specific serum, and BALF IgE levels and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay, and Th17 cells was evaluated by flow cytometry (FCM). Our study demonstrated that BA inhibited OVA-induced increases in RI and eosinophil count; interleukin (IL)-4, IL-17A levels, and Cdyn were recovered and increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that BA substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue. FCM studies demonstrated that BA substantially inhibited Th17 cells. These findings suggest that BA may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma., (Copyright © 2013 John Wiley & Sons, Ltd.)

Aim of the Study: Sceptridium ternatum Lyon (ST), a common Chinese herb, has been used in treatment of allergic asthma and whooping cough. In the present study, we investigated the Th1/Th2 ratio of peripheral blood and mRNA levels of leukotriene receptors after the treatment of ST in allergic asthma mouse model., Materials and Methods: Mouse asthma model was developed by ovalbumin (OVA) sensitization followed by the inhalation of aerosol allergen. Montelukast (10mg/kg), as a positive control drug, and ST were administrated six days before the OVA sensitization for ten days. Airway responsiveness was evaluated by the Medlab 12.0 biological signal processing system. The ratio of Th1/Th2 cells was determined by flow cytometry. The expression level of Cyslt1 was measured by PCR. Pathological changes of lung tissues were examined by H&E staining., Results: ST significantly reduced the airway responsiveness, elevated the ratio of Th1/Th2, and decreased Cyslt1 mRNA level in a dose-dependent manner. High-dose ST distinctly prevented the pathological changes of lung tissues., Conclusion: High-dose ST had the same efficacy as Montelukast in a mouse asthma model, and ST could be a potential anti-asthmatic agent., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Asthma is an inflammatory disease where the balance between Th1/Th2 and Th17/Treg plays a crucial role in its pathogenesis. Shikonin is used to treat a variety of autoimmune diseases due to its good anti-inflammatory activity. However, the effect and mechanism of shikonin on asthma remain unknown.

Abstract Background According to the Th1/Th2 paradigm, the expansion of Th1-type clones in individuals with type 1 diabetes results in reduced Th2-type clones, preventing the development of atopic diseases and vice versa. However, there is no consensus regarding the direct or inverse relationship between autoimmune and atopic diseases. Objective The aim of this scoping review was to examine the knowledge gap about the possibility of coexistence of asthma and type 1 diabetes and determine the prevalence of this association. Methods A scoping review was conducted, following the proposal of the Joanna Briggs Institute. The Population, Concept, and Context strategy was used to formulate the guiding question. The proposed question was: “What is the prevalence of asthma in people with T1DM?” After excluding duplicate articles, analyzing titles and abstracts, and excluding articles that did not answer the guiding question, 17 articles remained and were included in this review. Results Most of the articles selected conformed to the Th1/Th2 hypothesis, as the prevalence of asthma was lower in individuals with T1DM. However, similar or higher prevalence of asthma was found between cases and controls in few articles. Conclusion The prevalence of asthma in people with T1DM ranged from 1.7% to 23.1%. Maybe the mechanisms that characterizes the Th1/Th2 paradigm aren’t as simple as just the interaction of certain cytokines, since Th1-mediated autoimmune diseases and Th2- mediated atopy can coexist.

Background: According to the Th1/Th2 paradigm, the expansion of Th1-type clones in individuals with type 1 diabetes results in reduced Th2-type clones, preventing the development of atopic diseases and vice versa. However, there is no consensus regarding the direct or inverse relationship between autoimmune and atopic diseases. Objective: The aim of this scoping review was to examine the knowledge gap about the possibility of coexistence of asthma and type 1 diabetes and determine the prevalence of this association. Methods: A scoping review was conducted, following the proposal of the Joanna Briggs Institute. The Population, Concept, and Context strategy was used to formulate the guiding question. The proposed question was: "What is the prevalence of asthma in people with T1DM?" After excluding duplicate articles, analyzing titles and abstracts, and excluding articles that did not answer the guiding question, 17 articles remained and were included in this review. Results: Most of the articles selected conformed to the Th1/Th2 hypothesis, as the prevalence of asthma was lower in individuals with T1DM. However, similar or higher prevalence of asthma was found between cases and controls in few articles. Conclusion: The prevalence of asthma in people with T1DM ranged from 1.7% to 23.1%. Maybe the mechanisms that characterizes the Th1/Th2 paradigm aren't as simple as just the interaction of certain cytokines, since Th1-mediated autoimmune diseases and Th2- mediated atopy can coexist. [ABSTRACT FROM AUTHOR]

Some research has shown that PM2.5 causes Th1/Th2 immune imbalance and aggravates asthma. However, the exact mechanism of PM2.5 causing aggravation of asthma remains unclear. The purpose of this study was to investigate whether exposure to PM2.5 exacerbates Th1/Th2 immune imbalance through the Notch signaling pathway. Eight-week-old SPF female BALF/c mice were sensitized by ovalbumin to establish an asthma mouse model. PM2.5 exposure was carried out by aerosol inhalation of PM2.5 (510 μg/m3) after each provocation. The lung function of mice was measured and Splenic T lymphocyte subsets were detected. Notch signaling pathway was tested. The levels of interferon (IFN)-γ and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid were determined. The results showed that the expression of the mRNA and protein of Notch1 and Hes1 in the asthma group were significantly higher than those in healthy controls. The levels of IL-4 were also remarkably high; while the levels of IFN-γ were remarkably low in serum and BALF, the Th1% and Th1/Th2 ratios were significantly lower, and Th2% was significantly higher in the asthma group than in the healthy controls. PM2.5 promoted further activation of the Notch signaling pathway and aggravated Th1/Th2 immune imbalance in asthmatic mice. γ-secretase inhibitor can partially inhibit the activation of the Notch signaling pathway and alleviate aggravation of immune imbalance. In conclusion, the asthmatic mice had a Th1/Th2 immune imbalance and an overactivated Notch signaling pathway. PM2.5 further aggravated Th1/Th2 immune imbalance by activating the Notch signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Background Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action. Methods In vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4+ T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested. Results GITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children. Conclusions This study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4+ T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma.

BACKGROUND: Severe asthma is a major burden on health-economic resources; hence, knoing the epidemiology of these patients is important in planning and provision of asthma care. In addition, identifying and managing the comorbidities helps improve symptoms and reduce associated morbidity and mortality. OBJECTIVES: Epidemiology of difficult asthma has not been ell studied in the Middle East, so in this study, e present the demographic and clinical characteristics of severe asthma in the United Arab Emirates (UAE). METHODS: We retrospectively revieed the notes of severe asthma patients attending three tertiary care hospitals beteen May 2015 and December 2019. Data on baseline demographics, asthma characteristics, treatment, and comorbidities ere collected. RESULTS: We revieed the notes of 458 patients (271 females and 187 males) that fulfilled the 2019 Global Initiative for Asthma guidelines for the diagnosis of severe asthma. The mean age as 47.7 (standard deviation 17.2) years. Males had significantly higher asthma control test scores (17.9 vs. 16, P = 0.01) and mean blood eosinophils (0.401 vs. 0.294, P

BACKGROUND: Severe asthma is a major burden on health-economic resources; hence, knoing the epidemiology of these patients is important in planning and provision of asthma care. In addition, identifying and managing the comorbidities helps improve symptoms and reduce associated morbidity and mortality. OBJECTIVES: Epidemiology of difficult asthma has not been ell studied in the Middle East, so in this study, e present the demographic and clinical characteristics of severe asthma in the United Arab Emirates (UAE). METHODS: We retrospectively revieed the notes of severe asthma patients attending three tertiary care hospitals beteen May 2015 and December 2019. Data on baseline demographics, asthma characteristics, treatment, and comorbidities ere collected. RESULTS: We revieed the notes of 458 patients (271 females and 187 males) that fulfilled the 2019 Global Initiative for Asthma guidelines for the diagnosis of severe asthma. The mean age as 47.7 (standard deviation 17.2) years. Males had significantly higher asthma control test scores (17.9 vs. 16, P = 0.01) and mean blood eosinophils (0.401 vs. 0.294, P <0.01) than females. The most common comorbidity observed as allergic rhinitis (52.2%) folloed by gastroesophageal reflux disease (27.1%). In total, 109 (23.8%) patients ere on biological therapies ith most patients being on omalizumab and dupilumab (29 and 18 patients, respectively). Most patients ere nonsmokers (97.2%), and majority ere of TH2-high phenotype (75.7%). CONCLUSIONS: In this first report of severe asthma characteristics in the UAE, e found a pattern of female preponderance and most patients having a Th2-high phenotype. The findings are likely to help optimize asthma care in the region in the era of biologic therapies. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action.Methods: In vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4+ T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested.Results: GITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children.Conclusions: This study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4+ T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma. [ABSTRACT FROM AUTHOR]

Background Asthma is a chronic inflammatory disease of the airways characterized by involvement of a variety of inflammatory cells. Asthma is associated with imbalances between Th1/Th2 cells and their characteristic cytokine profiles. Nigella sativa is a plant that possesses immunomodulatory and anti-inflammatory properties. Objective To investigate the potential anti-asthmatic effect of Nigella sativa oil on Th1/Th2 cells, IFN-ɣ/IL-4 cytokines, and improvement of asthma control. Methods Children aged 6-15 years with asthma in Dr. Saiful Anwar Hospital, Malang, were enrolled in this study. All patients were treated based on standard treatment guidelines for asthma. Nigella sativa oil (NSO) was given per oral as supplementary treatment at a dose of 15-30 mg/kg/day for 8 weeks, in a randomized, single-blind, controlled trial. Peripheral Th1 and Th2 cells were counted by flow cytometry and IFN-ɣ and IL-4 cytokines were measured by ELISA. Improvement of asthma control was assessed by the asthma control test (ACT) score. Results Twenty-eight patients completed the study, 14 in the NSO treatment group and 14 in standard treatment group. No significant differences were found in the number of Th1 and Th2 cells, or in the Th1/Th2 ratio between groups after treatment (P=0.074, P=0.481, and P=0.265, respectively). Compared to the control, the NSO group showed a significant elevation of IFN-ɣ (P=0.046) and reduction of IL-4 (P=0.002). At the end of study, ACT score was not significantly different between groups (P=0.413). Conclusion Supplementation with Nigella sativa oil improves IFN-ɣ/IL-4 balance and asthma control in children with asthma.

Background: Asthma, a common respiratory disease, is harmful biological effect to our health. As a traditional Chinese medicine for asthma, Majie cataplasm could alleviate the symptoms of asthma and its compositions have immunomodulatory effects. Previous experiments showed that Majie cataplasm was an effective approach to mitigate asthma airway remodeling and had the potential to regulate Th2 cytokines of IL-5 and IL-13. Therefore, our further research focuses on the explanation about the regulatory effect of Majie cataplasm on reshaping Th1/Th2 through their related transcription factors. Methods: In this experiment, the launch of asthma model was made by inducing with Ovalbumin (OVA) in C57 mice (n = 40), including 4 groups: the untreated control group (n = 10), the asthma model group (n = 10), the dexamethasone group (n = 10) and the Majie cataplasm group (n = 10). After the intervention, all groups of animals got detected for serum IgE levels, and HE staining of lung tissues was to observe and examine pathological changes. Meanwhile, we analyzed the secretion of IL-4+ T cells and IFN-γ+ T cells in spleen by flow cytometry. The expressions of transcription factor STAT6 mRNA, GATA-3 mRNA and T-bet mRNA in lung tissues was tested by PCR, and western blot had been used to detect levels of JAK2 and STAT3. Results: We found that Majie cataplasm eased the content of serum IgE and lung inflammation. It could lower the increased number of IL-4+ T cells and IFN-γ+ T cells (P < 0.0001, P < 0.01) in asthmatic mice and curb the expression of STAT6 mRNA and GATA-3 (P < 0.0001, P < 0.01) mRNA as well as the protein levels of JAK2 (P < 0.001) and the ratio of pSTAT3/STAT3 (P < 0.05). Besides, Majie cataplasm made its mark on T-bet mRNA by improving it (P < 0.0001). Conclusion: These data suggest that Majie cataplasm exert an anti-inflammatory effect of Th2 by rebalancing Th1/Th2 through corresponding transcription factor STAT6, GATA-3, STAT3, and T-bet, which providing a strong cornerstone for asthma control. [ABSTRACT FROM AUTHOR]

Background There is now increasing evidence that asthma and atopy originate in part in utero, with disease risk being associated with the altered epigenetic regulation of genes. Objective and Methods To determine the relationship between variations in DNA methylation at birth and the development of allergic disease, we examined the methylation status of CpG loci within the promoter regions of Th1/2 lineage commitment genes ( GATA3, IL-4, IL-4R, STAT4 and TBET) in umbilical cord DNA at birth in a cohort of infants from the Southampton Women's Survey (n = 696) who were later assessed for asthma, atopic eczema and atopy. Results We found that higher methylation of GATA3 CpGs −2211/−2209 at birth was associated with a reduced risk of asthma at ages 3 (median ratio [median methylation in asthma group/median methylation in non-asthma group] = 0.74, P = .006) and 6-7 (median ratio 0.90, P = .048) years. Furthermore, we demonstrated that the GATA3 CpG loci associated with later risk of asthma lie within a NF-κB binding site and that methylation here blocks transcription factor binding to the GATA3 promoter in the human Jurkat T-cell line. Associations between umbilical cord methylation of CpG loci within IL-4R with atopic eczema at 12 months (median ratio 1.02, P = .028), and TBET with atopy (median ratio 0.98, P = .017) at 6-7 years of age were also observed. Conclusions and Clinical Relevance Our findings provide further evidence of a developmental contribution to the risk of later allergic disorders and suggest that involvement of epigenetic mechanisms in childhood asthma is already demonstrable at birth. [ABSTRACT FROM AUTHOR]

Garlic (Allium sativum L.) has been used extensively as a food ingredient and medicinally, but the effect on asthmatic airway inflammation has not been studied in detail. We accordingly explored the protective effects exerted by various garlic fraction extracts against airway inflammation with Dermatophagoides pteronyssinus (Der p)−induced allergic asthma in vivo and in vitro. Garlic extraction was realized using n-hexane, dichloromethane, ethylacetate, n-butanol, and water in sequence to obtain different fraction extracts. Mice were orally administered different fractions (80 mg/kg) daily for four weeks. The histological results showed that the water fraction could ameliorate lung-based goblet cell hyperplasia, inflammatory cell infiltration, and mucus hypersecretion. The water fraction extracts decreased IgE and IgG1, and they decreased inflammatory cells as quantified in bronchoalveolar lavage fluid (BALF); however, they increased IgG2a in serum. Moreover, the water fraction extracts increased IFN-γ and IL-12 (both constituting Th1 cytokines) in BALF, but they reduced IL-13, -4, and -5 (all constituting Th2 cytokines), and also inhibited the expression of IL-1β, IL-6, and TNF-α. The water fraction also inhibited the PI3K/Akt/NF-κB signal pathways in A549 cells. These findings suggest that water fraction extracts of garlic have a clear anti-inflammatory effect on Der p−induced allergic asthma.

Objective To evaluate the relationship of high mobility group box 1 (HMGB1) and TLR4 with airway inflammation and the role of vitamin D. Methods Totally 24 BALB/c mice were randomly divided into control group, asthma group, and 1,25-(OH)2D3 group, each having 8 mice. The pathological changes in lung tissue of the mice were observed by hematoxylin-eosin (HE) staining, bronchial wall thickness was measured with computer pathological image analysis system software. The expressions of HMGB1 and TLR4 in lung tissue were detected by immunohistochemical method. Bronchoalveolar lavage fluid (BALF) was collected for cytological examination; the contents of HMGB1, TLR4, IL-4 and IFN-γ in BALF and the peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Results The expressions of HMGB1 and TLR4 in lung tissue were stronger in asthma group, but weaker in intervention group. The total number of leukocytes as well as the percentages of eosinophils, neutrophils and lymphocytes increased significantly in BALF in asthma group, but significantly decreased in intervention group (all P<0.05). The ratio of monocyte/macrophage significantly decreased in asthma group, but increased significantly in intervention group (P<0.05). The contents of HMGB1, TLR4 and IL-4 in BALF and the peripheral blood were significantly higher in asthma group than in control and intervention groups, whereas IFN-γ level was significantly lower than that in control and intervention groups (all P<0.05). HMGB1 and TLR4 contents had a positive correlation with the total number of cells and IL-4 concentration in BALF, respectively (r1=0.796, 0.730; r2=0.695, 0.648; all P<0.05). Conclusion HMGB1 and TLR4 were associated with airway inflammation and immune disorders. An appropriate amount of 1,25-(OH)2D3 can relieve airway inflammation, which may be associated with regulating Th1/Th2 cells balance. [ABSTRACT FROM AUTHOR]

In this review we discuss the role of dendritic cells (DC) in the pathogenesis of allergic contact hypersensitivity (ACH) and atopic disorders, such as asthma and atopic eczema. In ACH patients, DC recognize the invasion of simple chemicals such as haptens, and trigger antigen-specific T cell responses leading to the characteristic histological and clinical changes such as spongiosis and papulovesicular eruptions. During atopic disorders, it is well known that the Th2-deviated immune response plays a crucial role in their pathogenesis. DC provide T cells with antigen and costimulatory signals (signals 1 and 2, respectively), as well as with a polarizing signal (signal 3). When studying ACH, it is important to understand how simple chemicals induce the activation of DC and their migration to the draining lymph nodes where they supply signals 1 and 2 to naïve T cells. The mechanisms by which DC induce the Th2-deviated immune response, namely via the Th2-deviated signal 3, are central topics in the pathogenesis of atopic disorders.

Dendritic cells (DCs) are associated with the activation and differentiation of T helper (Th) cells. Cluster of differentiation (CD)80 and CD86, the co-stimulatory molecules highly expressed in DCs, have are prominent in promoting the differentiation of Th cells toward Th2 cells. However, little is known about the effect of CD80 and CD86 knockdown on Th1/Th2 cytokine production in mature DCs (mDCs). The aim of the present study was to investigate whether small-interfering RNA (siRNA) could suppress the surface expression of CD80 and CD86 in mDCs. The effects of CD80 and CD86 knockdown in mDCs on Th1/Th2 cytokine expression were examined using an asthmatic murine model. DCs were isolated, separated and cultured in vitro. Flow cytometry was used to examine the expression of CD11c, CD80 and CD86 on the DCs. The DCs were transfected with CD80- and CD86-specific siRNA, while non-siRNA and negative siRNA controls were also designed. Then, the mRNA and protein expression levels of CD80 and CD86 were determined by reverse transcription-quantitative polymerase chain reaction and flow cytometry, respectively. The levels of interferon (IFN)-γ and interleukin (IL)-4 produced by T cells co-cultured with mDCs were measured by enzyme-linked immunosorbent assay. Substantial downregulation of CD80 and CD86 mRNA and protein levels were observed in the mDCs following transfection with siRNA. The level of IFN-γ produced by T cells co-cultured with mDCs was significantly increased in the siRNA group, while IL-4 production was significantly decreased. These results show that specific targeting of CD80 and CD86 with siRNA is able to suppress CD80/CD86 expression and consequently regulate Th1/Th2 cytokine levels by increasing IFN-γ production and decreasing IL-4 levels in an asthmatic murine model. [ABSTRACT FROM AUTHOR]

Background: The increase in the incidence of allergic disorders especially in developed countries may be explained by the hygiene hypothesis. A novel therapeutic approach that causes a Th1-dominant response under conditions of Th2-skewed immunity has been investigated. Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a widely used anti-tuberculosis vaccine that strongly induces a Th1-predominant immune response. A potential role for BCG in the treatment of allergic diseases has been reported. In the present study, we investigated whether subcutaneous inoculation with a low dose (1 × 105) of BCG vaccine can attenuate allergic inflammation of the airway in a murine model of asthma. Methods: Female BALB/c mice were vaccinated on day 0 with a subcutaneous. injection of 1 × 105 CFU of BCG, and sensitized to ovalbumin (OVA, i.p., with alum) on day 7 and 14, respectively. After a 2-week interval, they were exposed to aerosolized OVA (1%). In another experiment, BCG-sensitized splenic CD4+ T cells were adoptively transferred before sensitization. Results: We found that BCG-vaccinated mice had fewer eosinophils in BALF and less severe allergic inflammation. The expression of IL-4 as well as Eotaxin and TARC was down-regulated in the vaccinated mice, while that of both IL-12 and IFN-γ was up-regulated. Moreover, the transfer of splenic CD4+ T cells from vaccinated mice into naive mice before OVA-sensitization prevented the development of allergic inflammation. These splenic CD4+ T cells produced much IFN-γ. Conclusions: The subcutaneous administration of (low-dose) BCG vaccine suppressed allergic inflammation via Th1-skewed immunity and might have clinical applications in immunotherapy for asthma.

Introduction In China, acupuncture which is part of traditional Chinese medicine is effectively used for the treatment of asthma. This study was designed to evaluate the effect of acupuncture on airway inflammation and the associated cytokines produced by different Th mouse subtypes induced by chronic ovalbumin (OVA) inhalation. Methods A mouse asthma model was induced by OVA exposure. Mice were divided into 4 groups: normal control, asthma model, acupuncture and sham acupuncture groups, and acupoints GV14, BL12, BL13 and BL23 were selected for acupuncture treatment. Airway hyperresponsiveness (AHR) was analysed using Buxco RC system. Pulmonary histopathology analysis was performed by H&E staining. The inflammatory mediators assay in bronchoalveolar lavage fluid (BALF) and serum were investigated by ELISA and Bio-Plex. Results Our results demonstrated that acupuncture reduced AHR to methacholine (Mch) of OVA-induced asthma mice, attenuated inflammatory cells infiltration into lung and mucus secretion. Analysis of cytokines revealed that Th1 cytokine IFN-γ elevated in both BALF and serum by acupuncture treatment. Meanwhile, Th2 cytokines such as IL-4 and IL-5 levels both in BALF and serum reduced significantly compared to mice exposure to OVA. IL-17A was inhibited by acupuncture and IL-10 which is produced by Treg cells increased in BALF both by acupuncture and sham acupuncture. However, TGF-β as another mediator produced by Treg cells did not change markedly by acupuncture treatment. Conclusion This study indicated that acupuncture treatment appeared to be effective in attenuating inflammation in mice chronically exposed to OVA. This protective effect of acupuncture might be associated with regulation of immune responses by elevating Th1 and Treg cytokines and decreasing Th2 and Th17 cytokines. This may indicate that acupuncture has a regulatory effect with the ability of resetting the Th1/Th2 and Th17/Treg balance. Changes induced resulting from needling requires further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Astragaloside IV is the chief ingredient of Radix Astragali, which has been used in the Traditional Chinese Medicine as a major component of many polyherbal formulations for the repair and regeneration of injured organ and tissues. We tested the anti-asthmatic effects of AST IV and the possible mechanisms. BALB/c mice that were sensitized and challenged to ovalbumin (OVA) were treated with AST IV (40mg/kg and 20mg/kg) 1h before they were challenged with OVA. Our study demonstrated that AST IV inhibited OVA-induced increases in eosinophil count; interleukin (IL)-4 level were recovered in bronchoalveolar lavage fluid increased IFN-γ and IL-10 levels in bronchoalveolar lavage fluid. Histological studies demonstrated that AST IV substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that AST IV substantially increased CD4+CD25+Foxp3 T cells (Treg). Furthermore quantitative real-time (qPCR) studies demonstrated that AST IV substantially enhanced Foxp3 mRNA expression in lung tissue. These findings suggest that AST IV may effectively ameliorate the progression of airway inflammation and could be used as a therapy for patients with allergic inflammation. [Copyright &y& Elsevier]

Background: Asthma is a complex airway disease involving a variety of cells and cytokines. Xanthium sibiricum Patrin ex Widder (X. sibiricum) is a traditional Chinese medicine for various immune diseases, especially allergic rhinitis and asthma. Sesquiterpene lactones are the main bioactive and most abundant constituent, and are characteristic component of the plant. We explore whether sesquiterpene lactones from X. sibiricum (SL-XS) is the main active constitute for its anti-asthma activity.Purpose: In the present study, SL-XS was isolated, the major compounds were isolated and identified in extract of SL-XS, and the anti-asthma activity of SL-XS was validated in vivo.Methods: SL-XS was isolated by a standard phytochemical method. The structures of major sesquiterpene lactones were identified by NMR and LC-MS spectra. The contents of major SL-XS were analyzed by HPLC. The anti-asthma effect of SL-XS was evaluated in a house dust mite (HDM)-induced mouse model.Results: The sesquiterpene lactones were isolated from X. sibiricum, and five major constituents i.e., 8‑epi-xanthatin-1β, 5β-epoxide (1), tomentosin (2), 8‑epi-xanthatin (3), 2‑epi-xanthumin (4) and sibiriolide B (5) were identified from SL-XS. Oral administration of SL-XS dose-dependently ameliorated airway inflammation and remodeling in HDM-challenged asthma mouse model. Furthermore, SL-XS treatment inhibited the upregulation of proinflammatory and Th2 cytokines, while reversed the downregulation of Th1 related cytokines. In addition, SL-XS regulated the balance between T-bet and GATA-3. Moreover, SL-XS inhibited the upregulation of JAK1, p-JAK1, JAK2, p-JAK2, JAK3, p-JAK3 and p-STAT6 in HDM-challenged mice.Conclusion: The sesquiterpene lactones including five major constituents may be the main anti-asthma active constituent of X. sibiricum. SL-XS exerted its anti-asthma effect by modulating the Th1/Th2 balance via the JAK/STAT signaling pathway. [ABSTRACT FROM AUTHOR]

Background. Obesity is a risk factor for asthma. Studies in mice suggest that the adipokines leptin and adiponectin affect asthmatic responses. The purpose of this study was to determine if adipokines associated with obesity are (1) altered in obese women with asthma compared to controls and (2) associated with increased cytokines and chemokines involved in allergic inflammation. Methods. We performed a cross-sectional study of asthmatic and non-asthmatic obese premenopausal women. Participants answered questionnaires and performed lung function tests. Serum and peripheral blood mononuclear cells (PBMCs) were collected for analysis of cytokines and adipokines. Results. A total of 22 asthmatic (mean body mass index 40.0 ± 5.1 kg/m2) and 20 non-asthmatic women (mean body mass index 41.3 ± 5.6 kg/m2) participated. We found no difference in serum adipokine concentrations between asthmatics and non-asthmatics. Serum adiponectin correlated positively with PBMC eotaxin (rs = 0.55, p = .0003) and RANTES (regulated upon activation, normal T-cell expressed, and secreted) (rs = 0.36, p = .03), whereas serum leptin correlated negatively with PBMC eotaxin (rs = -0.34, p = .04). There was a negative correlation between serum adiponectin and PBMC interferon-γ (rs = -0.41, p = .01). Conclusions. Perturbations of adipokines that occur in obesity were correlated with decreased cytokine production typically associated with allergic responses in PBMC of obese premenopausal women. This study suggests that although obese asthmatics may have elements of Th2-mediated inflammation, adipokine derangements in obesity are associated with Th1 rather than Th2 bias. Obesity has complex effects on allergic inflammation and is likely to be important modifier of the pathogenesis of airway disease in asthma. [ABSTRACT FROM AUTHOR]

Background and objective: Stable asthma is characterized by the production of Th2 cytokines, although Th1 cytokines may play a key role in aspects such as airway hyper-responsiveness. This study explored cytokine profiles associated with asthma exacerbation. Methods: Intracellular T-cell cytokine production was measured in 16 children with acute severe asthma (emergency department), after convalescence (6 weeks, n = 13), with stable disease (after 6 months, n = 7) and in 14 age-matched hospital controls. Flow cytometry was used to identify CD4+ and CD8+ cells and to quantify intracellular T-cell production of the cytokines interferon (IFN)-γ, IL-4 and IL-13. Cytokine production was compared using analysis of variance and random-effects generalized linear models and associations were examined using Pearson's correlation. Results: Cytokine production was evident in CD4+ and CD8+ cells, and compared with asthmatic children, non-asthmatics had a higher percentage of IFN-γ+CD4+ cells ( P = 0.01). The percentage of CD8+IFN-γ+ cells was increased in the convalescent phase compared with acute ( P = 0.009) and stable asthma ( P = 0.004). IL-4+ cells were not significantly altered. IL-13 levels were higher in acute disease than in stable asthma ( P = 0.009 in CD4+ cells) and IFN-γ/IL-13 ratios indicated a Th2 profile during exacerbation ( P = 0.005 in CD4+ cells). Conclusions: IL-13, rather than IL-4, may play a pro-inflammatory role during acute severe asthma, whereas IFN-γ responses were associated with recovery from acute severe asthma. These results suggest that altered T-cell cytokine profiles may contribute to the pathogenesis of and recovery from asthma exacerbations. [ABSTRACT FROM AUTHOR]

We showed in a previous study that hot-water extracts of Agaricus blazei (Agaricus extracts) had anti-tumor activity to Meth A fibrosarcoma, but it remains unclear whether the Agaricus extracts ameliorate the skewed balance of type-1 T helper (Th1) and type-2 T helper (Th2) cells. We examined whether Agaricus extracts effect the skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice. When Meth A-bearing mice were given orally either Agaricus extracts or water once a day starting 5 days after tumor implantation, spleen T cells, prepared from tumor-bearing mice treated with Agaricus extracts, in response to anti-CD3 monoclonal antibody produced significantly higher levels of interferon γ (IFN-γ) than that of controls. The mRNA expression of IFN-γ-inducing protein 10 and the frequency of CD69+ or CD49d+ cells, among activated T cells infiltrated into tumors, significantly increased in Agaricus-treated mice, compared with those of tumor-controls. In asthma-induced mice, treatment with the Agaricus extracts caused significant downregulation of OVA-specific antibody responses of IgG1 and IgE but not of IgG2a, and significantly decreased total cell numbers, levels of interleukin 5, and eosinophil numbers in bronchial alveolar lavage fluids. IFN-γ production by anti-CD3-stimulated spleen cells, obtained from Agaricus-treated mice, significantly increased. Our results strongly suggest that oral administration of Agaricus extracts ameliorates the Th1/Th2 balance from the Th2-skewed conditions. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (tubercle bacilli) and the related acid-fast bacteria including Mycobacterium bovis Bacille Calmett–Guerin (BCG) have a characteristic cell wall (CW) containing various lipoglycans and glycolipids. Such lipoglycans have been reported to activate type-I inflammatory responses via dendritic cells (DCs) through Toll-like receptor 2. In this study, lipoglycans, lipoarabinomannan (LAM), lipomannan (LM) and phosphatidylinositol mannoside (PIM), were purified from the CW fractions of M. bovis BCG Tokyo-172, and the effect on the differentiation of human peripheral blood naive CD4 T cells into Th1 and Th2 was examined. LAM/LM molecules enhanced Th1 differentiation under both Th1 and Th2 conditions, whereas some other glycolipids and phospholipid enhanced Th2 differentiation under Th2 conditions. Other components had little effect under the given conditions. Even in highly purified CD4 T cell cultures, LAM/LM enhanced Th1 generation only under Th1 culture conditions. These results indicate that LAM/LM possesses a potent augmenting activity in Th1 differentiation in human CD4 T cells. LAM/LM appeared to act directly on naive CD4 T cells to enhance Th1 differentiation under Th1 culture conditions, while acting indirectly to up-regulate the generation of Th1 cells via IL-12/DCs under Th1 and Th2 conditions. Therefore, these results provide the first evidence indicating that LAM/LM from M. bovis BCG may possess a potent modulating activity in the human system, and thus supporting the strategy for the use of BCG components in the vaccine development for such Th2 diseases as allergic asthma and rhinitis. [ABSTRACT FROM PUBLISHER]

Background Cockroach allergens play a very important role in allergic diseases, especially asthma. The major allergen of the American cockroach ( Periplaneta americana), Per a 3, naturally occurs as isoforms of hexamers. Objective The aim of this study was to investigate whether the hexameric structures of Per a 3 influence their allergenicity and immunogenicity. Methods Therefore, we compared the different effects of native hexamers and dissociated monomers of cockroach haemolymph (HL), containing almost only Per a 3 proteins (HL-Per a 3), on proliferation and T-helper type 1 (Th1)/Th2 cytokine production of human CD4+ T cells in co-culture with allergen-pulsed monocyte-derived autologous dendritic cells (DC) as well as the leukotriene release of basophils. Results In P. americana-sensitized and non-sensitized donors the HL-Per a 3 monomers were internalized faster by immature DC and induced higher proliferation and IFN-γ production than the hexamers. While in non-sensitized donors IL-4 and IL-5 as well as IL-10 production were also increased after stimulation with monomeric HL-Per a 3-pulsed DC, Th2 cytokine and IL-10 production were only enhanced in P. americana-sensitized donors using hexameric HL-Per a 3-pulsed DC. Furthermore, in the leukotriene release assay the monomers were less effective than the hexamers. Conclusion Our data indicate that the quaternary structure can influence both allergenicity and immunogenicity, also depending on the sensitization status. The monomeric variant of Per a 3 allergens could be a possible candidate for a specific immunotherapy because the IgE-mediated allergic reaction and the Th2-inducing capacity are diminished while the Th1-inducing capacity is retained. [ABSTRACT FROM AUTHOR]

In this review we discuss the role of dendritic cells (DC) in the pathogenesis of allergic contact hypersensitivity (ACH) and atopic disorders, such as asthma and atopic eczema. In ACH patients, DC recognize the invasion of simple chemicals such as haptens, and trigger antigen-specific T cell responses leading to the characteristic histological and clinical changes such as spongiosis and papulovesicular eruptions. During atopic disorders, it is well known that the Th2-deviated immune response plays a crucial role in their pathogenesis. DC provide T cells with antigen and costimulatory signals (signals 1 and 2, respectively), as well as with a polarizing signal (signal 3). When studying ACH, it is important to understand how simple chemicals induce the activation of DC and their migration to the draining lymph nodes where they supply signals 1 and 2 to naíve T cells. The mechanisms by which DC induce the Th2-deviated immune response, namely via the Th2-deviated signal 3, are central topics in the pathogenesis of atopic disorders. [ABSTRACT FROM AUTHOR]

Txk/Rlk, a member of the Tec family of tyrosine kinases, is an important signaling mediator. We previously reported that human Txk is expressed in Th1/Th0 cells, and Txk translocates from cytoplasm into nuclei upon activation. Txk regulates specifically interferon-γ gene transcription. Txk, poly(ADP-ribose) polymerase 1, and elongation factor 1α make a complex to bind to interferon-γ gene promoter region-53/-39 (Txk responsive element) to exert positive effects on transcription as a Th1 cell-associated transcription factor. Txk expression is enhanced in rheumatoid arthritis and Behçet's disease, where Th1 dominant immunity occurs. In bronchial asthma and atopic dermatitis, typical Th2 diseases, Txk expression is reduced. Modulation of Txk expression by gene transfer or similar modality may lead to the correction of aberrant immunity and, consequently, disease treatment. [ABSTRACT FROM AUTHOR]

The role of the type-2 T helper (Th2) cell-mediated immune response in the immunopathogenesis of atopic dermatitis (AD) is well documented. Whether polarized immunoresponse is confined to antigen-specific T cells or is distributed among all T cell subsets is still controversial. We investigated frequencies of interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) producing CD3(+) and CD4(+) T cells in peripheral blood from children with atopic dermatitis and healthy subjects with and without in vitro stimulation. Children with severe AD had a significantly lower percentage of CD4(+) T cells spontaneously expressing IL-4 compared with healthy controls (p <0.01). Polyclonal stimulation significantly increased cytokine production in both AD patients and healthy individuals. Frequencies of CD3(+) and CD4(+) producing IL-2, IL-4, IFN-gamma, and TNF-alpha after in vitro stimulation with phorbol-12-myristate 13-acetate (PMA) + ionomycin were comparable in the AD and control groups. In response to PMA/ionomycin, children with AD and asthma symptoms had a significantly lower percentage of CD3(+) T cells producing TNF-alpha. We failed to demonstrate evidence of an imbalance with respect to type-2 cytokine productions in children with AD. Comparable induction of Th1 and Th2 cytokines in polyclonally stimulated peripheral CD3(+) and CD4(+)T cells from AD patients and controls puts into question the polarized Th2 immune response as a general characteristic of T cells in children with atopic dermatitis. [ABSTRACT FROM AUTHOR]