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

Kento Sawane; Takahiro Nagatake; Koji Hosomi; So-Ichiro Hirata; Jun Adachi; Yuichi Abe; Junko Isoyama; Hidehiko Suzuki; Ayu Matsunaga; Satoshi Fukumitsu; Kazuhiko Aida; Takeshi Tomonaga; Makoto Arita; Jun Kunisawa

doi:10.3390/nu11122868

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

Nutrients. 2019 Nov 22;11(12):2868. doi: 10.3390/nu11122868.

Authors

Kento Sawane^{1

2

3}, Takahiro Nagatake², Koji Hosomi², So-Ichiro Hirata^{2

4}, Jun Adachi⁵, Yuichi Abe⁶, Junko Isoyama⁵, Hidehiko Suzuki², Ayu Matsunaga², Satoshi Fukumitsu^{1

7}, Kazuhiko Aida¹, Takeshi Tomonaga⁵, Makoto Arita^{8

9

10}, Jun Kunisawa^{2

3

4

11

12}

Affiliations

¹ Nippon Flour Mills Co., Ltd., Innovation Center, Kanagawa 243-0041, Japan.
² 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.
³ Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
⁴ Department of Microbiology and Immunology, Kobe University Graduate School of Medicine, Hyogo 650-0017, Japan.
⁵ Laboratory of Proteome Research, NIBIOHN, Osaka 567-0085, Japan.
⁶ Division of Molecular Diagnosis, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
⁷ Collaborative Graduate School Program, University of Tsukuba, Ibaraki 305-8577, Japan.
⁸ Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan.
⁹ Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
¹⁰ Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan.
¹¹ Graduate School of Medicine and Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan.
¹² 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.

Abstract

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.

Keywords: PPAR; eosinophil; lipid metabolism; nasal allergy; omega-3 fatty acids.

MeSH terms

Administration, Intranasal
Animals
Anti-Allergic Agents / metabolism
Anti-Allergic Agents / pharmacology*
Disease Models, Animal
Eicosapentaenoic Acid / analogs & derivatives*
Eicosapentaenoic Acid / metabolism
Eicosapentaenoic Acid / pharmacology
Eosinophils / drug effects
Eosinophils / metabolism*
Female
Inflammation / drug therapy
Linseed Oil / administration & dosage
Lipid Metabolism
Mice
Mice, Inbred C57BL
PPAR gamma / metabolism*
Rhinitis, Allergic / drug therapy*

Substances

Anti-Allergic Agents
PPAR gamma
Linseed Oil
15-hydroxy-5,8,11,13,17-eicosapentaenoic acid
Eicosapentaenoic Acid

Abstract

MeSH terms

Substances

Grants and funding