CCL5 induces a pro-inflammatory profile in microglia in vitro

Cell Immunol. 2011;270(2):164-71. doi: 10.1016/j.cellimm.2011.05.001. Epub 2011 May 26.

Abstract

The chemokine receptors CCR1, CCR2, CCR3, CCR5, and CXCR2 have been found to be expressed on microglia in many neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease. There is emerging evidence that chemokines, besides chemoattraction, might directly modulate reactive profiles of microglia. To address this hypothesis we have investigated the effects of CCL2, CCL3, CCL5, and CXCL1 on cytokine and growth factor production, NO synthesis, and phagocytosis in non-stimulated and lipopolysaccharide-stimulated primary rat microglia. The respective receptors CCR1, CCR5, and CXCR2 were shown to be functionally expressed on microglia. All tested chemokines stimulated chemotaxis whereas only CCL5 increased NO secretion and attenuated IL-10 as well as IGF-1 production in activated microglia. Based on these findings we propose that besides its chemoattractant function CCL5 has a modulatory effect on activated microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemokine CCL2 / pharmacology
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / metabolism
  • Chemokine CCL3 / pharmacology
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Chemokine CCL5 / pharmacology*
  • Chemokine CXCL1 / genetics
  • Chemokine CXCL1 / metabolism
  • Chemokine CXCL1 / pharmacology
  • Chemotaxis / drug effects
  • DNA Primers / genetics
  • In Vitro Techniques
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / pharmacology
  • Insulin-Like Growth Factor I / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Microglia / drug effects*
  • Microglia / immunology*
  • Microglia / metabolism
  • Nitric Oxide / biosynthesis
  • Phagocytosis / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, CCR1 / metabolism
  • Receptors, Interleukin-8B / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Ccl2 protein, rat
  • Ccr1 protein, rat
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL5
  • Chemokine CXCL1
  • Cxcl1 protein, rat
  • DNA Primers
  • Inflammation Mediators
  • RNA, Messenger
  • Receptors, CCR1
  • Receptors, Interleukin-8B
  • Recombinant Proteins
  • Interleukin-10
  • Nitric Oxide
  • Insulin-Like Growth Factor I