Effect of compound Maqin decoction on TGF-?1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

Effect of compound Maqin decoction on TGF-?1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

Genet Mol Res. 2016 Sep 2;15(3):

Authors: Xie YH, Li XP, Xu ZX, Qian P, Li XL, Wang YQ

Abstract
In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-?1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-?1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-?1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-?1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-?1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.

PMID: 27706676 [PubMed – in process]

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Effect of different helminth extracts on the development of asthma in mice: the influence of early-life exposure and the role of IL-10 response.

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Effect of different helminth extracts on the development of asthma in mice: the influence of early-life exposure and the role of IL-10 response.

Exp Parasitol. 2015 Jun 17;

Authors: Pitrez PM, Gualdi LP, Barbosa GL, Sudbrack S, Ponzi D, Cao RG, Silva AC, Machado DC, Jones MH, Stein RT, Graeff-Teixeira C

Abstract
It is not currently clear whether different parasites have distinct effects on the airway inflammatory response in asthma and whether exposure in early life to helminths have a stronger impact in a potential inhibitory effect on asthma. The aim of this study is to evaluate the effect of exposure to different helminth extracts on the development of allergic pulmonary response in mice, including early-life exposure. Different helminth extracts (Angiostrongylus costaricensis, Angiostrongylus cantonensis and Ascaris lumbricoides) were studied in female adult BALB/c and C57BL/6 IL-10-deficient mice in a protocol of murine asthma, injected intraperitoneally in different periods of exposure (early, pre-sensitization and post-sensitization). Cell counts in bronchoalveolar lavage (BAL), eosinophil peroxidase (EPO) from lung tissue, cytokine levels from BAL/spleen cell cultures, and lung histology were analyzed. Airway cellular influx induced by OVA was significantly inhibited by extracts of A. cantonensis and A. lumbricoides. Extracts of A. lumbricoides and A. costaricensis led to a significant reduction of IL-5 in BAL (p<0.001). Only the exposure to A. lumbricoides led to an increased production of IL-10 in the lungs (p<0.001). In IL-10-deficient mice exposed to A. costaricensis pre-sensitization, eosinophil counts and IL-5 levels in BAL and EPO in lung tissue were significantly reduced. In the early exposure to A. cantonensis, lung inflammation was clearly inhibited. In conclusion, different helminth extracts inhibit allergic lung inflammation in mice. IL-10 may not play a central role in some helminth-host interactions. Early exposure to helminth extracts could be a potential strategy to explore primary prevention in asthma.

PMID: 26093162 [PubMed – as supplied by publisher]

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IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma.

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma.

J Immunol. 2014 Dec 19;

Authors: Böhm L, Maxeiner J, Meyer-Martin H, Reuter S, Finotto S, Klein M, Schild H, Schmitt E, Bopp T, Taube C

Abstract
Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3(+), and IL-10-producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, thymic Foxp3(+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.

PMID: 25527785 [PubMed – as supplied by publisher]

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