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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Main Authors: Yasunori Konno, Shigeharu Ueki, Masahide Takeda, Yoshiki Kobayashi, Mami Tamaki, Yuki Moritoki, Hajime Oyamada, Masamichi Itoga, Hiroyuki Kayaba, Ayumi Omokawa, Makoto Hirokawa
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4366258?pdf=render
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author Yasunori Konno
Shigeharu Ueki
Masahide Takeda
Yoshiki Kobayashi
Mami Tamaki
Yuki Moritoki
Hajime Oyamada
Masamichi Itoga
Hiroyuki Kayaba
Ayumi Omokawa
Makoto Hirokawa
author_facet Yasunori Konno
Shigeharu Ueki
Masahide Takeda
Yoshiki Kobayashi
Mami Tamaki
Yuki Moritoki
Hajime Oyamada
Masamichi Itoga
Hiroyuki Kayaba
Ayumi Omokawa
Makoto Hirokawa
author_sort Yasunori Konno
collection DOAJ
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.
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spelling doaj.art-b92d3da68f8441868f1832d2994868b62022-12-22T00:21:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012038610.1371/journal.pone.0120386Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.Yasunori KonnoShigeharu UekiMasahide TakedaYoshiki KobayashiMami TamakiYuki MoritokiHajime OyamadaMasamichi ItogaHiroyuki KayabaAyumi OmokawaMakoto HirokawaRecent 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.http://europepmc.org/articles/PMC4366258?pdf=render
spellingShingle Yasunori Konno
Shigeharu Ueki
Masahide Takeda
Yoshiki Kobayashi
Mami Tamaki
Yuki Moritoki
Hajime Oyamada
Masamichi Itoga
Hiroyuki Kayaba
Ayumi Omokawa
Makoto Hirokawa
Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.
PLoS ONE
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
url http://europepmc.org/articles/PMC4366258?pdf=render
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