Tim-3 enhances brain inflammation by promoting M1 macrophage polarization following intracerebral hemorrhage in mice

Int Immunopharmacol. 2017 Dec:53:143-148. doi: 10.1016/j.intimp.2017.10.023.

Abstract

Macrophage polarization contributes to brain inflammation following spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) has been identified to induce macrophage mediated inflammation following ICH. However, the regulation of Tim-3 on macrophage polarization following ICH has not been fully studied. In current experiment, we explored Tim-3 expression, macrophage polarization, brain water content and neurological function in WT and Tim-3-/- ICH mice. In addition, downstream transcriptional factor TRIF and IRF3 were also analyzed. We found that ICH promoted Tim-3 expression and M1 polarization in the perihematomal region of WT mice, leading to increased brain water content and neurological impairment. However, deletion of Tim-3 expression attenuated M1 polarization, decreased rain water content and improved neurological function of ICH mice. Furthermore, Tim-3 signal promoted transcriptional factors TRIF and IRF3 levels, regulating macrophage polarization. The data suggested that Tim-3 played a crucial role in the macrophage polarization and brain inflammation following ICH, and might represent a promising way in ICH therapy.

Keywords: ICH; Inflammation; M1 polarization; Tim-3.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Cell Differentiation
  • Cerebral Hemorrhage / immunology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Encephalitis / immunology*
  • Gene Expression Regulation
  • Hepatitis A Virus Cellular Receptor 2 / genetics
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Humans
  • Interferon Regulatory Factor-3 / metabolism
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Targeted Therapy
  • Th1 Cells / immunology

Substances

  • Adaptor Proteins, Vesicular Transport
  • Cytokines
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • TICAM-1 protein, mouse