Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia

Background: several g-protein-coupled receptors (gpcrs) have been shown to be important signaling mediators between neurons and glia. in our previous screening for identification of nerve injury-associated gpcrs,g-protein-coupled receptor 84 (gpr84) mrna showed the highest up-regulation by microglia after nerve injury. gpr84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model,yet its function in resident microglia in the central nervous system is poorly understood. methods: we used endogenous,natural,and surrogate agonists for gpr84 (capric acid,embelin,and 6-oau,respectively) and examined their effect on mouse primary cultured microglia in vitro. results: 6-n-octylaminouracil (6-oau),embelin,and capric acid rapidly induced membrane ruffling and motility in cultured microglia obtained from c57bl/6 mice,although these agonists failed to promote microglial pro-inflammatory cytokine expression. concomitantly,6-oau suppressed forskolin-induced increase of camp in cultured microglia. pertussis toxin,an inhibitor of gi-coupled signaling,completely suppressed 6-oau-induced microglial membrane ruffling and motility. in contrast,no 6-oau-induced microglial membrane ruffling and motility was observed in microglia from dba/2 mice,a mouse strain that does not express functional gpr84 protein due to endogenous nonsense mutation of the gpr84 gene. conclusions: gpr84 mediated signaling causes microglial motility and membrane ruffling but does not promote pro-inflammatory responses. as gpr84 is a known receptor for medium-chain fatty acids,those released from damaged brain cells may be involved in the enhancement of microglial motility through gpr84 after neuronal injury. © 2017 the author(s).