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Eosinophils are recruited to the intestinal mucosa in substantial numbers in food allergen-driven gastrointestinal (GI) inflammation. Soluble epoxide hydrolase (sEH) is known to play a pro-inflammatory role during inflammation by metabolizing anti-inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. We investigated the role of sEH in a murine model of food allergy and evaluated the potential therapeutic effect of a highly selective sEH inhibitor (trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]-cyclohexyloxy}-benzoic acid [t-TUCB]). Oral exposure of mice on a soy-free diet to soy protein isolate (SPI) induced expression of intestinal sEH, increased circulating total and antigen-specific IgE levels, and caused significant weight loss. Administration of t-TUCB to SPI-challenged mice inhibited IgE levels and prevented SPI-induced weight loss. Additionally, SPI-induced GI inflammation characterized by increased recruitment of eosinophils and mast cells, elevated eotaxin 1 levels, mucus hypersecretion, and decreased epithelial junction protein expression. In t-TUCB-treated mice, eosinophilia, mast cell recruitment, and mucus secretion were significantly lower than in untreated mice and SPI-induced loss of junction protein expression was prevented to variable levels. sEH expression in eosinophils was induced by inflammatory mediators TNF-\u03b1 and eotaxin-1. Treatment of eosinophils with t-TUCB significantly inhibited eosinophil migration, an effect that was mirrored by treatment with 11,12-EET, by inhibiting intracellular signaling events such as ERK (1\/2) activation and eotaxin-1-induced calcium flux. These studies suggest that sEH induced by soy proteins promotes allergic responses and GI inflammation including eosinophilia and that inhibition of sEH can attenuate these responses.<\/jats:p><jats:p>Soy protein-induced soluble epoxide hydrolase promotes allergic responses, gastrointestinal inflammation and eosinophilia; pharmacological inhibition of this enzyme leads to attenuation of these responses.<\/jats:p>","DOI":"10.1002\/jlb.3ma1017-423r","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T14:52:50Z","timestamp":1516200770000},"page":"109-122","source":"Crossref","is-referenced-by-count":15,"title":["Inhibition of soluble epoxide hydrolase attenuates eosinophil recruitment and food allergen-induced gastrointestinal inflammation"],"prefix":"10.1093","volume":"104","author":[{"given":"Idil","family":"Bastan","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinical Sciences, University of Minnesota , St. Paul, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao Na","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mythili","family":"Dileepan","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yana G","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alonso G","family":"Guedes","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, University of Minnesota , St. Paul, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Hee","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Entomology, University of California , Davis, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce D","family":"Hammock","sequence":"additional","affiliation":[{"name":"Department of Entomology, University of California , Davis, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J","family":"Washabau","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, University of Minnesota , St. Paul, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savita P","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, Minnesota, 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