Equine ß-defensin 1 regulates cytokine expression and phagocytosis in S. aureus-infected mouse monocyte macrophages via the Paxillin-FAK-PI3K pathway

文献类型： 外文期刊

第一作者： Pei, Le

作者： Pei, Le;Hou, Yongyue;Feng, Ying;Li, Feng;Zhang, Yuemei;Song, Yue;Pei, Le;Su, Hong;Cao, Guifang;Liu, Kun

作者机构：

关键词： Equine ss-defensin 1; S. aureus infection; Macrophage Paxillin-FAK-PI3K pathway

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：5.6； 五年影响因子：5.6 ）

ISSN： 1567-5769

年卷期： 2023 年 123 卷

页码：

收录情况： SCI

摘要： ss-defensin-1 (BD-1) is a rich source of disulfide bonds and antibacterial peptides that exhibit direct bactericidal function. The expression of BD-1 is primarily induced by external stimulation and is known to correlate with TLR-mediated inflammation, suggesting its association with innate immune responses. Equine ss-defensin-1 (eBD-1) belongs to the BD-1 family. Our previous study demonstrated that eBD-1 enhances cytokine expression and promotes macrophage phagocytosis of S. aureus, although the underlying mechanism remains unknown. In this study, we utilized a PI-3K inhibitor (PKI-402) to treat eBD-1 -treated S. aureus-infected macrophages in vitro. Our results revealed that PKI-402 decreased the expression of eBD-1-promoted TNF-alpha, IL-6, CXCL10, CD40, RANTES, and p65 mRNA. To further investigate the relationship between eBD-1 and phagocytosis, we examined the expression of paxillin and Fc.RIII (CD16 receptor) using western blot and immunofluorescence techniques. Our findings demonstrated that eBD-1 enhanced CD16 and paxillin expression in S. aureus -infected macrophages. Considering the correlation between paxillin expression and focal adhesion kinase (FAK), we transfected FAK siRNA into macrophages and evaluated paxillin expression using western blot analysis. Additionally, we quantified the number of S. aureus phagocytosed by macrophages. The results indicated a reduction in both paxillin expression and the number of S. aureus phagocytosed by macrophages upon FAK siRNA treatment. Our study showed the eBD-1 promotes cytokine mRNA expression in S. aureus-infected macrophages regulated by PI-3KNF-.B pathway, and it increases macrophage phagocytosis of S. aureus associated with the FAK-paxillin signaling pathway.

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