Medium-chain Fatty Acid-sensing Receptor, GPR84, Is a Proinflammatory Receptor

作者：Suzuki Masakatsu^*; Takaishi Sachiko; Nagasaki Miyuki; Onozawa Yoshiko; Iino Ikue; Maeda Hiroaki; Komai Tomoaki; Oda Tomiichiro

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288(15): 10684-10691.

DOI：10.1074/jbc.M112.420042

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 [S-35]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 TNF alpha 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.

• 出版日期2013-4-12