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Protective Role of Matrix Metalloproteinase-2 in Allergic Bronchial Asthma.

ABSTRACT: Inflammation, reversible obstruction, and hyperresponsiveness of the airways are characteristic findings of bronchial asthma. Several evidence has demonstrated the involvement of matrix metalloproteinase-2 in allergic airway inflammation. Matrix metalloproteinase-2 may promote aberrant tissue remodeling in late stages of allergic airway inflammation. However, whether matrix metalloproteinase-2 is detrimental or protective in early stages of allergic airway inflammation remains unclear. To evaluate this here we compared the severity of allergic bronchial asthma between mice overexpressing human matrix metalloproteinase-2 and wild type mice. After sensitization and challenge with an allergen, mice overexpressing the human matrix metalloproteinase-2 showed a significant reduction in airway hyperresponsiveness and in the expression of Th2 cytokines and IgE compared to their wild type counterparts. An inhibitor of matrix metalloproteinases abolished this beneficial effect of human matrix metalloproteinase-2 overexpression. Allergen-sensitized and challenged human matrix metalloproteinase-2 transgenic mice had enhanced percentage of M1 macrophages with increased expression of inducible nitric oxide synthase and STAT1 activation in the lungs compared to their wild type counterparts. There was no difference in the percentage of regulatory T cells between mouse groups. The results of this study showed that matrix metalloproteinase-2 is protective in allergic bronchial asthma by promoting polarization of macrophages to M1 phenotype.

SUBMITTER: Takahashi Y

PROVIDER: S-EPMC6687911 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEosinophils (EOS) is one of the most important cells involved in the pathogenesis of chronic airway inflammation in asthma, and its apoptosis is part of the mechanisms of asthma. Therefore, this study aimed to observe the effect of Chinese medicine Wentong decoction (WTD) in EOS apoptosis in asthmatic rats. This work also explored the mechanism of WTD regulation in EOS apoptosis and provided a new target for clinical treatment of asthma.MethodsAsthmatic rats induced by ovalbumin were treated with WTD. Lung function of rats in each group was detected, and lung tissue pathology, EOS counts in blood and bronchoalveolar lavage fluid were observed. The degree of the EOS apoptosis in rats was detected. The expression content of interleukin (IL)-5, IL-10, chemokine (C-C motif) ligand 5 (CCL5), granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth factor beta 1 (TGF-β1), interferon (IFN)-γ, and other cytokines in rat serum and the genes of Eotaxin mRNA, Fas mRNA, FasL mRNA, Fas/FasL and Bcl-2 mRNA in the lung tissues were determined.ResultsWTD can reduced airway resistance in rat models and improved airway compliance. The pathological changes of lung tissue in WTD group were significantly alleviated, at the same time, WTD could reduce the EOS count in the blood and BALF smears of the asthmatic model rats. Compared with the model group, the apoptosis degree of EOS significantly increased in rats in the WTD group. The expression of IL-5, CCL5, and GM-CSF in the serum and the expression of Eotaxin mRNA, Bcl-2 mRNA in the lung tissues in rats in the WTD group rats decreased. Moreover, the expression of IL-10, TGF-β1, and IFN-γ in the serum and the expression of Fas mRNA, FasL mRNA in the lung tissues in rats in the WTD group rats increased compared with that in rats in the model group.ConclusionsWentong decoction may accelerate EOS apoptosis, reduce asthma inflammation, and alleviate the disease through regulating and controlling the factors related to the anti-apoptosis and pro-apoptosis.

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Protective Role of Matrix Metalloproteinase-2 in Allergic Bronchial Asthma.

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