Abstract
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.