G protein-coupled receptor 84, a microglia-associated protein expressed in neuroinflammatory conditions.
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.
Bouchard
Caroline
C
Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, Québec City, Québec, Canada G1V 4G2.
Pagé
Julie
J
Bédard
Andréanne
A
Tremblay
Pierrot
P
Vallières
Luc
L
D000818:Animals; D001921:Brain / Q000276:immunology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D019446:Endotoxemia / Q000276:immunology* / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D005938:Glucocorticoids; C507114:Gpr84 protein, mouse; D007375:Interleukin-1; D008070:Lipopolysaccharides; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone