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Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2013 Apr 12; Vol. 288 (15), pp. 10684-91. Date of Electronic Publication: 2013 Feb 28. - Publication Year :
- 2013
-
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.
- Subjects :
- Animals
CHO Cells
Cattle
Chemokine CXCL1 genetics
Chemokine CXCL1 metabolism
Cricetinae
Cricetulus
Fatty Acids genetics
Female
HEK293 Cells
Humans
Inflammation chemically induced
Inflammation genetics
Inflammation metabolism
Interleukin-8 biosynthesis
Interleukin-8 genetics
Lipopolysaccharides toxicity
Macrophages pathology
Rats
Rats, Inbred Lew
Receptors, Cell Surface antagonists & inhibitors
Receptors, Cell Surface genetics
Receptors, G-Protein-Coupled
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha metabolism
U937 Cells
Uracil analogs & derivatives
Uracil pharmacology
Fatty Acids metabolism
Macrophages metabolism
Receptors, Cell Surface metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 288
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23449982
- Full Text :
- https://doi.org/10.1074/jbc.M112.420042