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J Biol Chem. 2013 Apr 12;288(15):10684-91. doi: 10.1074/jbc.M112.420042. Epub 2013 Feb 28.

Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor.

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1
Frontier Research Laboratories, R&D Division, Daiichi Sankyo Company, Limited, Tokyo 140-871, Japan.

Abstract

G protein-coupled receptor 84 (GPR84) is a putative receptor for medium-chain fatty acids (MCFAs), whose pathophysiological roles have not yet been clarified. Here, we show that GPR84 was activated by MCFAs with the hydroxyl group at the 2- or 3-position more effectively than nonhydroxylated MCFAs. We also identified a surrogate agonist, 6-n-octylaminouracil (6-OAU), for GPR84. These potential ligands and the surrogate agonist, 6-OAU, stimulated [(35)S]GTP binding and accumulated phosphoinositides in a GPR84-dependent manner. The surrogate agonist, 6-OAU, internalized GPR84-EGFP from the cell surface. Both the potential ligands and 6-OAU elicited chemotaxis of human polymorphonuclear leukocytes (PMNs) and macrophages and amplified LPS-stimulated production of the proinflammatory cytokine IL-8 from PMNs and TNFα from macrophages. Furthermore, the intravenous injection of 6-OAU raised the blood CXCL1 level in rats, and the inoculation of 6-OAU into the rat air pouch accumulated PMNs and macrophages in the site. Our results indicate a proinflammatory role of GPR84, suggesting that the receptor may be a novel target to treat chronic low grade inflammation associated-disease.

PMID:
23449982
PMCID:
PMC3624448
DOI:
10.1074/jbc.M112.420042
[Indexed for MEDLINE]
Free PMC Article
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