Supervillin Contributes to LPS-induced Inflammatory Response in THP-1 Cell-derived Macrophages
Supervillin Contributes to LPS-induced Inflammatory Response in THP-1 Cell-derived Macrophages
复制标题
Supervillin 有助于 LPS™ 在 THP™1 Cell™ 衍生的巨噬细胞中诱导炎症反应。
DOI：
10.1007/s10753-021-01551-7
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发表时间：
2021-09-03
期刊：
影响因子：
5.1
通讯作者：
Li，Shengnan
中科院分区：
文献类型：
--
作者：
Zhou，Jun;Que，Yuhui;Li，Shengnan
超绒毛蛋白（Supervillin，SVIL）是一种肌动蛋白结合的膜结合蛋白，属于绒毛蛋白/凝溶胶蛋白家族。已有研究表明SVIL参与巨噬细胞运动的调节，脂多糖（lipopolysaccharide，LPS）可增加中性粒细胞SVIL mRNA的表达，但其机制尚不清楚。本研究探讨了LPS调节巨噬细胞SVIL表达的分子机制，以及SVIL在LPS诱导的炎症中的可能作用。结果发现，LPS可明显增加THP-1源性巨噬细胞SVIL mRNA和蛋白的表达。Resatorvid（Res）抑制TLR 4可显著逆转LPS诱导的SVIL表达。此外，ERK 1/2信号通路（通过U 0126或GDC-0994）和NF-κB（通过BAY）的抑制显著降低LPS诱导的SVIL表达。有趣的是，SVIL特异性shRNA下调SVIL在mRNA和蛋白水平上显著减弱了LPS诱导的IL-6、IL-1β和TNF-α的表达。SVIL基因敲减可使THP-1源性巨噬细胞G2/M期细胞比例降低，S & G 0 - 1期细胞比例增加，但对细胞活力无影响。以上结果表明，LPS通过激活TLR 4/NF-κB和ERK 1/2 MAPK途径诱导SVIL的表达，并且SVIL参与了LPS诱导的巨噬细胞IL-6、IL-1β和TNF-α上调的炎症反应。
AbstractSupervillin (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 & G0-1phase 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.