TRIM59 suppresses NO production by promoting the binding of PIAS1 and STAT1 in macrophages

Int Immunopharmacol. 2020 Dec;89(Pt A):107030. doi: 10.1016/j.intimp.2020.107030. Epub 2020 Oct 10.

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.

Keywords: COX2; JAK2-STAT1 pathways; Macrophage; Melanoma; TRIM59; iNOS.

MeSH terms

  • Animals
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Down-Regulation
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Janus Kinase 2 / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / transplantation
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Inhibitors of Activated STAT / genetics
  • Protein Inhibitors of Activated STAT / metabolism*
  • RAW 264.7 Cells
  • STAT1 Transcription Factor / metabolism*
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism*
  • Tumor Burden
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor-Associated Macrophages / metabolism
  • Tumor-Associated Macrophages / transplantation

Substances

  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Pias1 protein, mouse
  • Protein Inhibitors of Activated STAT
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Tnf protein, mouse
  • Trim59 protein, mouse
  • Tripartite Motif Proteins
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Jak2 protein, mouse
  • Janus Kinase 2