G protein-coupled receptor 84, a microglia-associated protein expressed in neuroinflammatory conditions

Glia. 2007 Jun;55(8):790-800. doi: 10.1002/glia.20506.


G protein-coupled receptor 84 (GPR84) is a recently discovered member of the seven transmembrane receptor superfamily whose function and regulation are unknown. Here, we report that in mice suffering from endotoxemia, microglia express GPR84 in a strong and sustained manner. This property is shared by subpopulations of peripheral macrophages and, to a much lesser extent, monocytes. The induction of GPR84 expression by endotoxin is mediated, at least in part, by proinflammatory cytokines, notably tumor necrosis factor (TNF) and interleukin-1 (IL-1), because mice lacking either one or both of these molecules have fewer GPR84-expressing cells in their cerebral cortex than wild-type mice during the early phase of endotoxemia. Moreover, when injected intracerebrally or added to microglial cultures, recombinant TNF stimulates GPR84 expression through a dexamethasone-insensitive mechanism. Finally, we show that microglia produce GPR84 not only during endotoxemia, but also during experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. In conclusion, this study reports the identification of a new sensitive marker of microglial activation, which may play an important regulatory role in neuroimmunological processes, acting downstream to the effects of proinflammatory mediators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Endotoxemia / immunology*
  • Endotoxemia / physiopathology
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Glucocorticoids / pharmacology
  • Interleukin-1 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Microglia / cytology
  • Microglia / drug effects
  • Microglia / immunology*
  • Monocytes / immunology
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / immunology*
  • Tumor Necrosis Factor-alpha / pharmacology


  • Glucocorticoids
  • Gpr84 protein, mouse
  • Interleukin-1
  • Lipopolysaccharides
  • Receptors, G-Protein-Coupled
  • Tumor Necrosis Factor-alpha
  • Dexamethasone