Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2017-10-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | http://link.springer.com/article/10.1186/s12974-017-0970-y |
| _version_ | 1818327201709293568 |
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| author | Li Wei Kyohei Tokizane Hiroyuki Konishi Hua-Rong Yu Hiroshi Kiyama |
| author_facet | Li Wei Kyohei Tokizane Hiroyuki Konishi Hua-Rong Yu Hiroshi Kiyama |
| author_sort | Li Wei |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T12:12:31Z |
| format | Article |
| id | doaj.art-75f1c6db1a1343dbb77743bdb85bf4a6 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-13T12:12:31Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-75f1c6db1a1343dbb77743bdb85bf4a62022-12-21T23:46:48ZengBMCJournal of Neuroinflammation1742-20942017-10-0114111210.1186/s12974-017-0970-yAgonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microgliaLi Wei0Kyohei Tokizane1Hiroyuki Konishi2Hua-Rong Yu3Hiroshi Kiyama4Department of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of MedicineDepartment of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of MedicineDepartment of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of MedicineCollege of Basic Medical Science, Chongqing Medical UniversityDepartment of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12974-017-0970-yG-protein-coupled receptor 84Pro-inflammatory responseMicroglia morphologyMicroglia motilityFatty acid |
| spellingShingle | Li Wei Kyohei Tokizane Hiroyuki Konishi Hua-Rong Yu Hiroshi Kiyama Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia Journal of Neuroinflammation G-protein-coupled receptor 84 Pro-inflammatory response Microglia morphology Microglia motility Fatty acid |
| title | Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia |
| title_full | Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia |
| title_fullStr | Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia |
| title_full_unstemmed | Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia |
| title_short | Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia |
| title_sort | agonists for g protein coupled receptor 84 gpr84 alter cellular morphology and motility but do not induce pro inflammatory responses in microglia |
| topic | G-protein-coupled receptor 84 Pro-inflammatory response Microglia morphology Microglia motility Fatty acid |
| url | http://link.springer.com/article/10.1186/s12974-017-0970-y |
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