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      Dietary ω-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating T h2 immune responses

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          Abstract

          Allergic conjunctivitis (AC) is one of the most common ocular surface diseases in the world. In AC, T helper type 2 (T h2) immune responses play central roles in orchestrating inflammatory responses. However, the roles of lipid mediators in the onset and progression of AC remain to be fully explored. Although previous reports have shown the beneficial effects of supplementation of ω-3 fatty acids in asthma or atopic dermatitis, the underlying molecular mechanisms are poorly understood. In this study, a diet rich in ω-3 fatty acids alleviated AC symptoms in both early and late phases without affecting T h2 immune responses, but rather by altering the lipid mediator profiles. The ω-3 fatty acids completely suppressed scratching behavior toward the eyes, an allergic reaction provoked by itch. Although total serum IgE levels and the expression levels of T h2 cytokines and chemokines in the conjunctiva were not altered by ω-3 fatty acids, eosinophil infiltration into the conjunctiva was dramatically suppressed. The levels of ω-6–derived proinflammatory lipid mediators, including those with chemoattractant properties for eosinophils, were markedly reduced in the conjunctivae of ω-3 diet–fed mice. Dietary ω-3 fatty acids can alleviate a variety of symptoms of AC by altering the lipid mediator profile.—Hirakata, T., Lee, H.-C., Ohba, M., Saeki, K., Okuno, T., Murakami, A., Matsuda, A., Yokomizo, T. Dietary ω-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating T h2 immune responses.

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          Most cited references64

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          The development of allergic inflammation.

          Allergic disorders, such as anaphylaxis, hay fever, eczema and asthma, now afflict roughly 25% of people in the developed world. In allergic subjects, persistent or repetitive exposure to allergens, which typically are intrinsically innocuous substances common in the environment, results in chronic allergic inflammation. This in turn produces long-term changes in the structure of the affected organs and substantial abnormalities in their function. It is therefore important to understand the characteristics and consequences of acute and chronic allergic inflammation, and in particular to explore how mast cells can contribute to several features of this maladaptive pattern of immunological reactivity.
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            Resolvins and protectins in inflammation resolution.

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              Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions

              The endogenous cellular and molecular mechanisms that control acute inflammation and its resolution are of wide interest. Using self-resolving inflammatory exudates and lipidomics, we have identified a new pathway involving biosynthesis of potent antiinflammatory and proresolving mediators from the essential fatty acid docosahexaenoic acid (DHA) by macrophages (MΦs). During the resolution of mouse peritonitis, exudates accumulated both 17-hydroxydocosahexaenoic acid, a known marker of 17S-D series resolvin (Rv) and protectin biosynthesis, and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid from endogenous DHA. Addition of either DHA or 14S-hydroperoxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid to activated MΦs converted these substrates to novel dihydroxy-containing products that possessed potent antiinflammatory and proresolving activity with a potency similar to resolvin E1, 5S,12R,18R-trihydroxyeicosa-6Z,8E,10E,14Z,16E-pentaenoic acid, and protectin D1, 10R,17S-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. Stable isotope incorporation, intermediate trapping, and characterization of physical and biological properties of the products demonstrated a novel 14-lipoxygenase pathway, generating bioactive 7,14-dihydroxydocosa-4Z,8,10,12,16Z,19Z-hexaenoic acid, coined MΦ mediator in resolving inflammation (maresin), which enhances resolution. These findings suggest that maresins and this new metabolome may be involved in some of the beneficial actions of DHA and MΦs in tissue homeostasis, inflammation resolution, wound healing, and host defense.
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                Author and article information

                Journal
                FASEB J
                FASEB J
                fasebj
                fasebj
                The FASEB Journal
                Federation of American Societies for Experimental Biology (Bethesda, MD, USA )
                0892-6638
                1530-6860
                March 2019
                01 November 2018
                01 November 2018
                : 33
                : 3
                : 3392-3403
                Affiliations
                [* ]Department of Ophthalmology, Juntendo University Graduate School of Medicine, Tokyo, Japan;
                []Department of Biochemistry, Juntendo University Graduate School of Medicine, Tokyo, Japan
                Author notes
                [1 ]Correspondence: Department of Biochemistry, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: yokomizo-tky@ 123456umin.ac.jp
                Article
                FJ_201801805R
                10.1096/fj.201801805R
                6404575
                30383446
                78ae4d8b-a0d2-4843-b052-b866c800f7de
                © The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 2.0 International (CC BY-NC-ND 2.0) ( https://creativecommons.org/licenses/by-nc-nd/2.0/) which permits noncommercial use, distribution, and reproduction in any medium, but prohibits the publication/distribution of derivative works, provided the original work is properly cited.

                History
                : 26 August 2018
                : 09 October 2018
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 72, Pages: 12
                Categories
                Research
                Custom metadata
                v1

                Molecular biology
                eicosanoid,inflammation,hay fever,lipidomics,fish oil
                Molecular biology
                eicosanoid, inflammation, hay fever, lipidomics, fish oil

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