title: Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.
abstract: 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.
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors: Yasunori
authors: Y
authors: Konno
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors: Shigeharu
authors: S
authors: Ueki
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors: Masahide
authors: M
authors: Takeda
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan; Department of Otolaryngology, Kansai Medical University, Shin-machi, Hirakata City, Osaka, Japan.
authors: Yoshiki
authors: Y
authors: Kobayashi
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors: Mami
authors: M
authors: Tamaki
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors: Yuki
authors: Y
authors: Moritoki
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors: Hajime
authors: H
authors: Oyamada
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan; Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Masamichi
authors: M
authors: Itoga
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan; Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Hiroyuki
authors: H
authors: Kayaba
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors: Ayumi
authors: A
authors: Omokawa
authors: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors: Makoto
authors: M
authors: Hirokawa
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D008744:Methylamines / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
chemical_list: C491901:FAS protein, human; C519853:FFAR4 protein, human; C515630:GW9508; C508598:IL4 protein, human; D008744:Methylamines; D011422:Propionates; D047428:Protein Kinase Inhibitors; D043562:Receptors, G-Protein-Coupled; D019014:fas Receptor; D015847:Interleukin-4; C505407:CASP3 protein, human; D053148:Caspase 3