E3 ubiquitin ligase tripartite motif 7 positively regulates the TLR4-mediated immune response via its E3 ligase domain in macrophages
E3 ubiquitin ligase tripartite motif 7 positively regulates the TLR4-mediated immune response via its E3 ligase domain in macrophages
复制标题
E3泛素连接酶三联基序7通过其E3连接酶结构域在巨噬细胞中正向调节TLR4介导的免疫反应
DOI：
10.1016/j.molimm.2019.01.015
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发表时间：
2019-05-01
影响因子：
3.6
通讯作者：
Nie, Shinan
中科院分区：
文献类型：
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作者：
Lu, Mingfeng;Zhu, Xuhui;Nie, Shinan
作为 E3 泛素连接酶的三联基序 (TRIM) 家族成员被认为是先天免疫和抗病毒反应的关键调节因子。然而，TRIM7 的作用仍然难以捉摸。在这里，我们提供了证据证明 TRIM7 在调节 TLR4 介导的先天反应中的重要性。详细来说，我们发现 TRIM7 在巨噬细胞等抗原呈递细胞中高度表达。 TRIM7 的敲低可明显抑制 LPS 诱导的巨噬细胞中 IFN-β、TNF-α 和 IL-6 的产生。相反，TRIM7 的强制表达可能对这些促炎细胞因子产生相反的作用。进一步分析表明，这种效应是由 TLR4 相关信号通路介导的，包括 MAPK、NF-κ B 和 IRF3 相关通路。 TRIM7 上 E3 连接酶结构域的截短可能会减少促炎细胞因子的产生，表明该结构域在调节 LPS 引发的先天反应中发挥着关键作用。综上所述，我们在此报告TRIM7可能通过巨噬细胞中的E3连接酶结构域促进TLR4介导的先天反应，这为TRIM7在先天免疫中的机制作用提供了新的见解。
Members of the tripartite motif (TRIM) family as E3 ubiquitin ligases have been regarded as critical regulators of innate immunity and antiviral response. However, the role of TRIM7 is still elusive. Here, we provide evidence for the importance of TRIM7 in regulation of the TLR4-mediated innate response. In detail, we find that TRIM7 is highly expressed in antigen-presenting cells like macrophages. Knockdown of TRIM7 clearly inhibits the LPS-induced production of IFN-beta, TNF-alpha and IL-6 in macrophages. Conversely, forced expression of TRIM7 could exert an opposite effect on these pro-inflammatory cytokines. Further analysis indicates that such effect is mediated by the TLR4-associated signaling pathways including MAPKs, NF-kappa B and IRF3-involved pathways. Truncation of the E3 ligase domain on TRIM7 may reduce the production of pro-inflammatory cytokines, suggesting a critical role of this domain in the regulation of LPS-initiated innate response. Taken together, we report here that TRIM7 may facilitate the TLR4-mediated innate response via its E3 ligase domain in macrophages, which provides new insight into the mechanistic role of TRIM7 in innate immunity.