Asthma is a chronic inflammatory disease of the airways, and IL-35 has been found to be involved in the pathogenesis of inflammatory diseases by mediating the inhibition of effector T cells. But the role of IL-35 on cell pyroptosis, which frequently occurs in inflammatory diseases, has not been elucidated. Therefore, the present study used a TNF-α-induced bronchial epithelial cell injury model to investigate the mechanism of IL-35 action on cell pyroptosis and asthma injury. The effects of IL-35 on cell activity, inflammatory factor levels, cell barrier damage and cell pyroptosis-related proteins were examined by CCK-8, ELISA, lucifer yellow permeability and Western blotting assay, respectively. Subsequently, following the activation of p38 MAPK signaling pathway by adding p38 agonist, the effect of IL-35 on TNF-α-induced bronchial epithelial cell injury was investigated. The results showed that IL-35 reduced TNF-α-induced cell injury, decreased inflammatory factors, improved cell permeability, and inhibited cell pyroptosis. More importantly, the effect of IL-35 on injured cells was reversed after p38 MAPK pathway was activated. In summary, IL-35 inhibited p38 MAPK pathway to suppress cell pyroptosis and thereby reduce asthma injury.
Background: Bronchial asthma is a common chronic inflammatory disease of the respiratory tract, whose pathogenesis involves a variety of factors. The purpose of this study was to explore the effect of traditional Chinese medicine Glycyrrhizin (Gly) on lipopolysaccharide (LPS)-induced inflammation and apoptosis of bronchial epithelial cells and its action mechanism. Methods: Gly (20 µM) was used to treat bronchial epithelial BEAS-2B cells stimulated with LPS. The expression of SRC and miR-146b-5p in BEAS-2B cells was modified by the respective transfections with pcDNA-SRC, miR-146b-5p mimic and miR-146b-5p inhibitor. STRING and Starbase online databases were used to predict the relationship between Gly, miR-146b-5p and SRC. Luciferase reporter assays were performed to verify the binding of miR-146b-5p to SRC. The viability, inflammatory response and apoptosis of BEAS-2B cells were examined by CCK-8, ELISA and Tunel assays respectively. The expressions of apoptosis-related proteins (Bcl-2, Bax, caspase3 and Cleaved-caspase3), SRC and miR-146b-5p were detected by qRT-PCR or western blotting. Results: Gly inhibited LPS-induced inflammation and apoptosis in BEAS-2B cells. The interaction between Gly and SRC was predicted by STRING. SRC expression was high in BEAS-2B cells stimulated with LPS and could be negatively regulated by Gly. Overexpression of SRC effectively alleviated the inhibitory effect of Gly on LPS-induced damages in BEAS-2B cells. In addition, results of luciferase reporter assays verified SRC as a direct target gene of miR-146b-5p. The expression level of miR-146b-5p was downregulated by LPS stimulation in BEAS-2B cells. Gly decreased the expression of SRC in LPS-stimulated BEAS-2B cells. These results could all be reversed by miR-146b-5p knockdown. Conclusion: Gly decreases the expression of SRC by upregulating the level of miR-146b-5p, thus alleviating the inflammation and apoptosis of bronchial epithelial cells treated with LPS. Our results provide a new theoretical basis for applying Gly to the clinical management of asthma.
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