Scavenger receptor SRA attenuates TLR4-induced microglia activation in intracerebral hemorrhage

J Neuroimmunol. 2015 Dec 15:289:87-92. doi: 10.1016/j.jneuroim.2015.10.006. Epub 2015 Oct 10.

Abstract

Scavenger receptor A (SRA) has been shown to participate in the pattern recognition of pathogen infection. However, its role in intracerebral hemorrhage has not been well defined. In this study, we detected SRA and TLR4 expression and inflammatory response of microglia treated with erythrocyte lysate in vitro, and observed the cerebral water content and neurological deficit of ICH mice in vivo. We found that SRA deficiency leads to greater sensitivity to erythrocyte lysate-induced inflammatory response. SRA down-regulated inflammatory response expression in microglia by suppressing TLR4-induced activation. Collectively, we have identified the molecular linkage between SRA and the TLR4 signaling pathways in ICH. And our results reveal that SRA has important clinical implications for TLR-targeted immunotherapeutical strategy in ICH.

Keywords: Intracerebral hemorrhage; Microglia; SRA; TLR4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain Edema / etiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Hemorrhage / complications*
  • Cerebral Hemorrhage / pathology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Erythrocytes / cytology
  • Erythrocytes / immunology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / metabolism*
  • Nervous System Diseases / etiology
  • RNA Interference / physiology
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Time Factors
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Cytokines
  • Scavenger Receptors, Class A
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4