{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:08:42Z","timestamp":1781766522926,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15H05897"],"award-info":[{"award-number":["15H05897"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15H05898"],"award-info":[{"award-number":["15H05898"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15H04648"],"award-info":[{"award-number":["15H04648"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005612","name":"Shionogi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005612","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Asthma is characterized by airway inflammation and obstruction with eosinophil infiltration into the airway. Arachidonic acid, an omega\u20106 fatty acid, is metabolized into cysteinyl leukotriene with pro\u2010inflammatory properties for allergic inflammation, whereas the omega\u20103 fatty acid eicosapentaenoic acid (EPA) and its downstream metabolites are known to have anti\u2010inflammatory effects. In this study, we investigated the mechanism underlying the counter\u2010regulatory roles of EPA in inflamed lungs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57BL6 mice were sensitized and challenged by ovalbumin (OVA). After EPA treatment, we evaluated the cell count of Bronchoalveolar lavage fluid (BALF), mRNA expressions in the lungs by q\u2010PCR, and the amounts of lipid mediators by liquid chromatography\u2010tandem mass spectrometry (LC\u2010MS\/MS)\u2010based lipidomics. We investigated the effect of the metabolite of EPA by in vivo and in vitro studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eicosapentaenoic acid treatment reduced the accumulation of eosinophils in the airway and decreased mRNA expression of selected inflammatory mediators in the lung. Lipidomics clarified the metabolomic profile in the lungs. Among EPA\u2010derived metabolites, 12\u2010hydroxy\u201017,18\u2010epoxyeicosatetraenoic acid (12\u2010OH\u201017,18\u2010EpETE) was identified as one of the major biosynthesized molecules; the production of this molecule was amplified by EPA administration and allergic inflammation. Intravenous administration of 12\u2010OH\u201017,18\u2010EpETE attenuated airway eosinophilic inflammation through downregulation of C\u2010C chemokine motif 11 (<jats:italic>CCL11<\/jats:italic>) mRNA expression in the lungs. In vitro, this molecule also inhibited the release of CCL11 from human airway epithelial cells stimulated with interleukin\u20104.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrated that EPA alleviated airway eosinophilic inflammation through its conversion into bioactive metabolites. Additionally, our results suggest that 12\u2010OH\u201017,18\u2010EpETE is a potential therapeutic target for the management of asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13297","type":"journal-article","created":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T11:43:57Z","timestamp":1504179837000},"page":"369-378","source":"Crossref","is-referenced-by-count":21,"title":["12\u2010OH\u201017,18\u2010Epoxyeicosatetraenoic acid alleviates eosinophilic airway inflammation in murine lungs"],"prefix":"10.1111","volume":"73","author":[{"given":"T.","family":"Mochimaru","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7460-1990","authenticated-orcid":false,"given":"K.","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Miyata","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Matsusaka","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Masaki","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kabata","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ueda","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Goto","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences The University of Tokyo Tokyo Japan"},{"name":"Pharmaceutical Research Center Shionogi &amp; Co. 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