Supervillin (SVIL) is an actin-binding and membrane-associated protein, which belongs to villin/gelsolin family. It has been reported that SVIL was involved in the regulation of macrophages’ movement and lipopolysaccharide (LPS) increased the SVIL mRNA expression in neutrophils, but the underlying mechanisms remain unknown. This work investigated the underlying molecular mechanisms of LPS regulating SVIL expression in macrophages and hence the possible role of SVIL in LPS-induced inflammation. We found that in THP-1-derived macrophages, LPS obviously increased SVIL mRNA and protein expression. Inhibition of TLR4 by Resatorvid (Res) remarkably reversed the LPS-induced SVIL expression. Additionally, inhibition of ERK1/2 signaling pathway (by U0126 or GDC-0994) and NF-κB (by BAY) significantly reduced the LPS-induced SVIL expression. Interestingly, down-regulation of SVIL by SVIL-specific shRNAs significantly attenuated the expression of IL-6, IL-1β & TNF-α induced by LPS at both mRNA and protein levels. Furthermore, we also observed that SVIL knockdown decreased the proportion of cells in G₂/M phase and increased the proportion of cells in S & G_0-1 phase of THP-1 derived macrophages, but did not influence the cell viability. Taken together, we demonstrated that LPS induced the expression of SVIL via activating TLR4/NF-κB and ERK1/2 MAPK pathways, and SVIL participated in the inflammatory response of LPS-induced IL-6, IL-1β and TNF-α upregulation in macrophages.

Supervillin (SVIL) 是一种肌动蛋白结合和膜相关蛋白，属于绒毛蛋白/凝溶胶蛋白家族。据报道，SVIL 参与调节巨噬细胞的运动，脂多糖 (LPS) 增加了中性粒细胞中 SVIL mRNA 的表达，但其潜在机制仍不清楚。这项工作研究了 LPS 调节巨噬细胞中 SVIL 表达的潜在分子机制，从而研究了 SVIL 在 LPS 诱导的炎症中的可能作用。我们发现在 THP-1 衍生的巨噬细胞中，LPS 明显增加了 SVIL mRNA 和蛋白质的表达。Resatorvid (Res) 对 TLR4 的抑制显着逆转了 LPS 诱导的 SVIL 表达。此外，抑制 ERK1/2 信号通路（通过 U0126 或 GDC-0994）和 NF-κB（通过 BAY）显着降低了 LPS 诱导的 SVIL 表达。有趣的是，SVIL 特异性 shRNA 对 SVIL 的下调显着减弱了 LPS 在 mRNA 和蛋白质水平上诱导的 IL-6、IL-1β 和 TNF-α 的表达。此外，我们还观察到 SVIL 敲低降低了 G 中细胞的比例₂ /M期和增加THP-1衍生巨噬细胞S&G _0-1期的细胞比例，但不影响细胞活力。综上所述，我们证明 LPS 通过激活 TLR4/NF-κB 和 ERK1/2 MAPK 通路诱导 SVIL 的表达，并且 SVIL 参与了 LPS 诱导的 IL-6、IL-1β 和 TNF-α 上调的炎症反应。巨噬细胞。