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.
Highlights
Allergic rhinitis is among the most common allergic diseases and is increasing in prevalence globally [1,2]
eicosapentaenoic acid (EPA), but2019, not11, docosahexaenoic acid (DHA), SoyOVA group (Figure 2). These results suggest that dietary fatty acid (FA) can7alter the FA composition in both the plasma and Nasal passage (NP) and that increased omega-3 FA levels in linseed oil-fed dietary
When bone marrow-derived eosinophils or neutrophils were activated with a calcium ionophore in the presence of EPA, the eosinophils produced more 15-hydroxyeicosapentaenoic acid (15-HEPE) than did the neutrophils (Figure 5F). These results suggest that eosinophils infiltrate the NP, where they regulate allergic rhinitis by producing 15-HEPE
Summary
Allergic rhinitis is among the most common allergic diseases and is increasing in prevalence globally [1,2]. Degranulated mast cells secrete chemical mediators, including histamine and lipid mediators, that induce the nasal responses of allergic rhinitis, including sneezing, itchiness, and rhinorrhea [5] Given these mechanistic processes, promising strategies to control allergic symptoms include the inhibition of Th2 differentiation, IgE production, mast cell degranulation, and the interaction between chemical mediators and their receptors. EPA-derived resolvin E1 promotes the resolution of allergic lung inflammation [17], and DHA-derived resolvin D1 reduces histamine responses in the eye and regulates conjunctival goblet cell secretion [18] These studies indicate that omega-3 FA-derived metabolites have potential to regulate inflammation and allergic disease. We evaluated the effect of dietary linseed oil on allergic rhinitis in the upper respiratory tract by using an OVA-induced nasal allergy model in mice
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