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The 17,18-epoxyeico...
The 17,18-epoxyeicosatetraenoic acid-G protein-coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques
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Nagatake, Takahiro (author)
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Shiogama, Yumiko (author)
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Inoue, Asuka (author)
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Kikuta, Junichi (author)
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Honda, Tetsuya (author)
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Tiwari, Prabha (author)
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Kishi, Takayuki (author)
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Yanagisawa, Atsushi (author)
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Isobe, Yosuke (author)
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Matsumoto, Naomi (author)
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Shimojou, Michiko (author)
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Morimoto, Sakiko (author)
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Suzuki, Hidehiko (author)
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Hirata, So-ichiro (author)
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- Steneberg, Pär (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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- Edlund, Helena, 1960- (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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Aoki, Junken (author)
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Arita, Makoto (author)
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Kiyono, Hiroshi (author)
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Yasutomi, Yasuhiro (author)
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Ishii, Masaru (author)
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Kabashima, Kenji (author)
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Kunisawa, Jun (author)
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(creator_code:org_t)
- MOSBY-ELSEVIER, 2018
- 2018
- English.
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In: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 142:2, s. 470-482.e12
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Abstract
Subject headings
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- Background: Metabolites of eicosapentaenoic acid exert various physiologic actions. 17,18-Epoxyeicosatetraenoic acid (17,18-EpETE) is a recently identified new class of antiallergic and anti-inflammatory lipid metabolite of eicosapentaenoic acid, but its effects on skin inflammation and the underlying mechanisms remain to be investigated. Objective: We evaluated the effectiveness of 17,18-EpETE for control of contact hypersensitivity in mice and cynomolgus macaques. We further sought to reveal underlying mechanisms by identifying the responsible receptor and cellular target of 17,18-EpETE. Methods: Contact hypersensitivity was induced by topical application of 2,4-dinitrofluorobenzene. Skin inflammation and immune cell populations were analyzed by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. Neutrophil mobility was examined by means of imaging analysis in vivo and neutrophil culture in vitro. The receptor for 17,18-EpETE was identified by using the TGF-alpha shedding assay, and the receptor's involvement in the anti-inflammatory effects of 17,18-EpETE was examined by using KO mice and specific inhibitor treatment. Results: We found that preventive or therapeutic treatment with 17,18-EpETE ameliorated contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques. 17,18-EpETE was recognized by G protein-coupled receptor (GPR) 40 (also known as free fatty acid receptor 1) and inhibited chemoattractant-induced Rac activation and pseudopod formation in neutrophils. Indeed, the antiallergic inflammatory effect of 17,18-EpETE was abolished in the absence or inhibition of GPR40. Conclusion: 17,18-EpETE inhibits neutrophil mobility through GPR40 activation, which is a potential therapeutic target to control allergic inflammatory diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- 17 18-Epoxyeicosatetraenoic acid
- G protein-coupled receptor 40
- omega 3 fatty acid
- contact persensitivity
- dermatitis
- neutrophil
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Nagatake, Takahi ...
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Shiogama, Yumiko
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Inoue, Asuka
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Kikuta, Junichi
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Honda, Tetsuya
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Tiwari, Prabha
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show more...
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Kishi, Takayuki
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Yanagisawa, Atsu ...
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Isobe, Yosuke
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Matsumoto, Naomi
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Shimojou, Michik ...
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Morimoto, Sakiko
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Suzuki, Hidehiko
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Hirata, So-ichir ...
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Steneberg, Pär
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Edlund, Helena, ...
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Aoki, Junken
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Arita, Makoto
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Kiyono, Hiroshi
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Yasutomi, Yasuhi ...
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Ishii, Masaru
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Kabashima, Kenji
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Kunisawa, Jun
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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Umeå University