Medium-chain Fatty Acid-sensing Receptor, GPR84, Is a Proinflammatory Receptor
| Autor: | Miyuki Nagasaki, Tomoaki Komai, Tomiichiro Oda, Ikue Iino, Hiroaki Maeda, Sachiko Takaishi, Masakatsu Suzuki, Yoshiko Onozawa |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
Agonist endocrine system medicine.drug_class Chemokine CXCL1 Immunology Receptors Cell Surface Inflammation CHO Cells Biology Biochemistry Receptors G-Protein-Coupled Proinflammatory cytokine Cricetulus Cricetinae GPR84 medicine Animals Humans Uracil Receptor Molecular Biology chemistry.chemical_classification Tumor Necrosis Factor-alpha Macrophages Fatty Acids Interleukin-8 Fatty acid Chemotaxis U937 Cells Cell Biology Rats Cell biology HEK293 Cells chemistry Rats Inbred Lew Cattle Female Tumor necrosis factor alpha medicine.symptom |
| Zdroj: | Journal of Biological Chemistry. 288:10684-10691 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|