TRIM59 通过促进 PIAS1 和 STAT1 在巨噬细胞中的结合来抑制 NO 的产生。
TRIM59 suppresses NO production by promoting the binding of PIAS1 and STAT1 in macrophages.
机构信息
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China; Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China; Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
出版信息
Int Immunopharmacol. 2020 Dec;89(Pt A):107030. doi: 10.1016/j.intimp.2020.107030. Epub 2020 Oct 10.
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 subunit2 (COX2) and TNFα. 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.
巨噬细胞可以分泌各种炎症介质，在肿瘤生长和转移中起重要作用。然而，调节炎症介质产生的机制尚不完全清楚。在这里，我们发现 TRIM59 可以抑制 NO 的产生和诱导型一氧化氮合酶（iNOS）、细胞色素 c 氧化酶亚基 2（COX2）和 TNFα 的表达。TRIM59 通过抑制 JAK2-STAT1 信号通路的激活来抑制一氧化氮（NO）的产生。在 LPS 刺激下，巨噬细胞中的 TRIM59 从细胞质转位到细胞核，并直接与 STAT1 结合。在这个过程中，TRIM59 可以招募更多的 PIAS1 与 STAT1 结合，抑制 STAT1 的激活。最后，TRIM59 修饰的巨噬细胞可以促进肿瘤生长。因此，TRIM59 通过促进巨噬细胞中 PIAS1 和 STAT1 的结合来抑制 NO 的产生，可能调节肿瘤的生长。
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