TRIM59 suppresses NO production by promoting the binding of PIAS1 and STAT1 in macrophages
TRIM59 suppresses NO production by promoting the binding of PIAS1 and STAT1 in macrophages
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TRIM59 通过促进巨噬细胞中 PIAS1 和 STAT1 的结合来抑制 NO 产生
DOI：
10.1016/j.intimp.2020.107030
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发表时间：
2020-12-01
影响因子：
5.6
通讯作者：
Yang, Rongcun
中科院分区：
文献类型：
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作者：
Su, Xiaomin;Zhang, Qianjing;Yang, Rongcun
巨噬细胞能够分泌多种炎症介质，在肿瘤生长和转移过程中发挥着至关重要的作用。然而，调控炎症介质生成的机制尚未完全明晰。在此，我们发现TRIM59能够抑制一氧化氮（NO）的生成，以及诱导型一氧化氮合酶（iNOS）、细胞色素C氧化酶亚基2（COX2）和肿瘤坏死因子α（TNFα）的表达。TRIM59对一氧化氮生成的抑制作用是通过抑制JAK2 - STAT1信号通路的激活来实现的。在脂多糖（LPS）刺激下，巨噬细胞中的TRIM59从细胞质转移至细胞核，并直接与STAT1结合。在此过程中，TRIM59能够募集更多的PIAS1与STAT1结合，从而抑制STAT1的激活。最终，经TRIM59修饰的巨噬细胞能够促进肿瘤生长。因此，TRIM59可能通过促进巨噬细胞中PIAS1与STAT1的结合来抑制一氧化氮的生成，进而对肿瘤生长起到调控作用。
Macrophages, which can secret various inflammation mediators, have an essential role in tumor growth and metastasis. However, the mechanism(s) to regulate the production of inflammation mediator is not completely clear. Here we found that TRIM 59 could inhibit the production of NO and the expression of inducible nitric oxide synthase (iNOS), cytochrome c oxidase subunit 2 (COX2) and TNF alpha. TRIM59 mediated suppression on nitric oxide (NO) production is through inhibiting the activation of JAK2-STAT1 signal pathway. In response to LPS, TRIM59 in macrophages was translocated from cytoplasm to nucleus and directly bound with STAT1. During this process, TRIM59 could recruit much more PIAS1 to bind with STAT1 to suppress the activation of STAT1. Finally, TRIM59 modified macrophages could promote tumor growth. Thus, TRIM59 mediated suppression on NO production by promoting the binding of PIAS1 and STAT1 in macrophages may regulate tumor growth.