Tetramethylpyrazine Alleviates Tight Junction Disruption of Bronchial Mucosal Epithelial Cells Caused by Interleukin-17 via Inhibiting Nuclear Factor-κB-p65/Tumor Necrosis Factor-α Signaling Pathway

Bronchial mucosal epithelial dysregulation and barrier disruption are involved in the initiation and development of acute lung injury (ALI). Some inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17) contribute to the pathological changes of ALI. However, the roles and relationship between TNF-α and IL-17 during the disruption of bronchial epithelial tight junction remain unclear. Tetramethylpyrazine (TMP) is confirmed to have beneficial functions in hemostasis, inflammation, and cell growth. Here, we demonstrated the protective effects of TMP on bronchial mucosal epithelial injury induced by IL-17. We showed that IL-17 stimulation markedly reduced occludin and zonula occludens-1 (ZO-1) expression in bronchial mucosal epithelial cells via the nuclear factor-κB-p65/TNF-α signaling pathway, including NF-κB-p65-triggered TNF-α gene transcription and expression. TMP obviously rescued IL-17-induced occludin and ZO-1 downregulation. Mechanically, TMP substantially suppressed NF-κB-p65 activation and NF-κB-p65-induced TNF-α production in bronchial mucosal epithelial cells caused by IL-17. Taken together, this study indicates that TMP has a protective effect on bronchial mucosal epithelial cell injury due to IL-17 induction by inhibiting the NF-κB-p65/TNF-α signaling pathway.