TRIB1 induces macrophages to M2 phenotype by inhibiting IKB-zeta in prostate cancer

Cell Signal. 2019 Jul:59:152-162. doi: 10.1016/j.cellsig.2019.03.017. Epub 2019 Mar 26.

Abstract

Immunotherapy has made great breakthroughs in the field of cancer. However, the immunotherapeutic effect of prostate cancer is unsatisfactory. We found that the expression of TRIB1 was significantly correlated with the infiltration of CD163+ macrophages in prostate cancer. This study focused on the effects of TRIB1 on macrophage polarization in the immune microenvironment of prostate cancer. RNA sequencing analysis demonstrated that TRIB1 has significant effects on the regulation of the nuclear factor (NF)-κB signaling pathway and downstream cytokines. Flow cytometry and enzyme-linked immunosorbent assay were used to examine THP-1 cells cultured in conditioned medium from prostate cancer cells overexpressing TRIB1 and showed that overexpression of TRIB1 promoted the secretion of CXCL2 and interleukin (IL)8 by PC3 cells, which increased the secretion of IL12 by THP-1 cells as well as the expression of CD163 on THP-1 cells. IKB-zeta, regulated by TRIB1, was expressed in PC3 cells but was barely detectable in DU145 cells. The reductions in CXCL2 and IL8 by the inhibition of TRIB1 were rescued by the deletion of IKB-zeta. Here we showed that TRIB1 promoted the secretion of cytokines from prostate cancer cells and induced the differentiation of monocytes/macrophages into M2 macrophages.

Keywords: CD163; IKB-zeta，IL8; Macrophage; Prostate cancer; TRIB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Chemokine CXCL2 / immunology
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Macrophage Activation
  • Macrophages / cytology
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-kappa B / immunology
  • PC-3 Cells
  • Prostatic Neoplasms / metabolism*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / physiology
  • Receptors, Cell Surface / metabolism
  • THP-1 Cells
  • Tumor Microenvironment / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • CXCL2 protein, human
  • Chemokine CXCL2
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Receptors, Cell Surface
  • TRIB1 protein, human
  • Protein Serine-Threonine Kinases