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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366258/ https://www.ncbi.nlm.nih.gov/pubmed/25790291 http://dx.doi.org/10.1371/journal.pone.0120386 |
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author | Konno, Yasunori Ueki, Shigeharu Takeda, Masahide Kobayashi, Yoshiki Tamaki, Mami Moritoki, Yuki Oyamada, Hajime Itoga, Masamichi Kayaba, Hiroyuki Omokawa, Ayumi Hirokawa, Makoto |
author_facet | Konno, Yasunori Ueki, Shigeharu Takeda, Masahide Kobayashi, Yoshiki Tamaki, Mami Moritoki, Yuki Oyamada, Hajime Itoga, Masamichi Kayaba, Hiroyuki Omokawa, Ayumi Hirokawa, Makoto |
author_sort | Konno, Yasunori |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-4366258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43662582015-03-23 Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis Konno, Yasunori Ueki, Shigeharu Takeda, Masahide Kobayashi, Yoshiki Tamaki, Mami Moritoki, Yuki Oyamada, Hajime Itoga, Masamichi Kayaba, Hiroyuki Omokawa, Ayumi Hirokawa, Makoto PLoS One Research Article 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. Public Library of Science 2015-03-19 /pmc/articles/PMC4366258/ /pubmed/25790291 http://dx.doi.org/10.1371/journal.pone.0120386 Text en © 2015 Konno et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Konno, Yasunori Ueki, Shigeharu Takeda, Masahide Kobayashi, Yoshiki Tamaki, Mami Moritoki, Yuki Oyamada, Hajime Itoga, Masamichi Kayaba, Hiroyuki Omokawa, Ayumi Hirokawa, Makoto Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis |
title | Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis |
title_full | Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis |
title_fullStr | Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis |
title_full_unstemmed | Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis |
title_short | Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis |
title_sort | functional analysis of free fatty acid receptor gpr120 in human eosinophils: implications in metabolic homeostasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366258/ https://www.ncbi.nlm.nih.gov/pubmed/25790291 http://dx.doi.org/10.1371/journal.pone.0120386 |
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