Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis
Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed...
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| creator | Konno, Yasunori Ueki, Shigeharu Takeda, Masahide Kobayashi, Yoshiki Tamaki, Mami Moritoki, Yuki Oyamada, Hajime Itoga, Masamichi Kayaba, Hiroyuki Omokawa, Ayumi Hirokawa, Makoto |
| description | Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system. |
| doi_str_mv | 10.1371/journal.pone.0120386 |
| format | Article |
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GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0120386</identifier><identifier>PMID: 25790291</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Allergies ; Analysis ; Apoptosis ; Apoptosis - drug effects ; Caspase ; Caspase 3 - metabolism ; Caspase-3 ; Cell activation ; Cell surface ; Chemotactic response ; Cytokines ; Degranulation ; Down-regulation ; Energy metabolism ; Enzyme-linked immunosorbent assay ; Eosinophils ; Eosinophils - drug effects ; Eosinophils - metabolism ; Eosinophils - physiology ; fas Receptor - metabolism ; Fatty acids ; Functional analysis ; G protein-coupled receptors ; Homeostasis ; Homeostasis - drug effects ; Humans ; Immune system ; Insulin resistance ; Interleukin 4 ; Interleukin-4 - metabolism ; Internal medicine ; Internalization ; Kinases ; Laboratories ; Leukocytes (eosinophilic) ; Lymphocytes T ; Medicine ; Membrane proteins ; Metabolism ; Methylamines - pharmacology ; mRNA ; Obesity ; Physiology ; Propionates - pharmacology ; Protein Kinase Inhibitors - pharmacology ; Proteins ; Receptors, G-Protein-Coupled - agonists ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; RNA ; Rodents ; Stimulation ; University graduates</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0120386-e0120386</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Konno et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Konno et al 2015 Konno et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c802t-bb77d45c8902f0134a42efeaf6caedfc281f5d662be2a3cf6295265ab180fe623</citedby><cites>FETCH-LOGICAL-c802t-bb77d45c8902f0134a42efeaf6caedfc281f5d662be2a3cf6295265ab180fe623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366258/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366258/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25790291$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bandeira de Melo, Christianne</contributor><creatorcontrib>Konno, Yasunori</creatorcontrib><creatorcontrib>Ueki, Shigeharu</creatorcontrib><creatorcontrib>Takeda, Masahide</creatorcontrib><creatorcontrib>Kobayashi, Yoshiki</creatorcontrib><creatorcontrib>Tamaki, Mami</creatorcontrib><creatorcontrib>Moritoki, Yuki</creatorcontrib><creatorcontrib>Oyamada, Hajime</creatorcontrib><creatorcontrib>Itoga, Masamichi</creatorcontrib><creatorcontrib>Kayaba, Hiroyuki</creatorcontrib><creatorcontrib>Omokawa, Ayumi</creatorcontrib><creatorcontrib>Hirokawa, Makoto</creatorcontrib><title>Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. 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GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25790291</pmid><doi>10.1371/journal.pone.0120386</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1664782514 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Allergies Analysis Apoptosis Apoptosis - drug effects Caspase Caspase 3 - metabolism Caspase-3 Cell activation Cell surface Chemotactic response Cytokines Degranulation Down-regulation Energy metabolism Enzyme-linked immunosorbent assay Eosinophils Eosinophils - drug effects Eosinophils - metabolism Eosinophils - physiology fas Receptor - metabolism Fatty acids Functional analysis G protein-coupled receptors Homeostasis Homeostasis - drug effects Humans Immune system Insulin resistance Interleukin 4 Interleukin-4 - metabolism Internal medicine Internalization Kinases Laboratories Leukocytes (eosinophilic) Lymphocytes T Medicine Membrane proteins Metabolism Methylamines - pharmacology mRNA Obesity Physiology Propionates - pharmacology Protein Kinase Inhibitors - pharmacology Proteins Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - metabolism RNA Rodents Stimulation University graduates |
| title | Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T13%3A42%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Functional%20analysis%20of%20free%20fatty%20acid%20receptor%20GPR120%20in%20human%20eosinophils:%20implications%20in%20metabolic%20homeostasis&rft.jtitle=PloS%20one&rft.au=Konno,%20Yasunori&rft.date=2015-03-19&rft.volume=10&rft.issue=3&rft.spage=e0120386&rft.epage=e0120386&rft.pages=e0120386-e0120386&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0120386&rft_dat=%3Cgale_plos_%3EA423858942%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1664782514&rft_id=info:pmid/25790291&rft_galeid=A423858942&rft_doaj_id=oai_doaj_org_article_b92d3da68f8441868f1832d2994868b6&rfr_iscdi=true |