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Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice

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Nippon Flour Mills Co., Ltd., Innovation Center, Kanagawa 243-0041, Japan
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Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan
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Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan
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Department of Microbiology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017, Japan
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Laboratory of Proteome Research, NIBIOHN, Osaka 567-0085, Japan
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Division of Molecular Diagnosis, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
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Collaborative Graduate School Program, University of Tsukuba, Ibaraki 305-8577, Japan
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Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan
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Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan
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Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan
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Graduate School of Medicine and Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan
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Division of Mucosal Immunology, Department of Microbiology and Immunology and International Research and Development Center for Mucosal Vaccines, the Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(12), 2868; https://doi.org/10.3390/nu11122868
Received: 19 October 2019 / Revised: 13 November 2019 / Accepted: 18 November 2019 / Published: 22 November 2019
The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis. View Full-Text
Keywords: omega-3 fatty acids; nasal allergy; eosinophil; lipid metabolism; PPAR omega-3 fatty acids; nasal allergy; eosinophil; lipid metabolism; PPAR
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Sawane, K.; Nagatake, T.; Hosomi, K.; Hirata, S.-I.; Adachi, J.; Abe, Y.; Isoyama, J.; Suzuki, H.; Matsunaga, A.; Fukumitsu, S.; Aida, K.; Tomonaga, T.; Arita, M.; Kunisawa, J. Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice. Nutrients 2019, 11, 2868.

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