期刊
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
卷 158, 期 4, 页码 375-386出版社
KARGER
DOI: 10.1159/000332965
关键词
Allergy; Apoptosis; Chemotaxis; Docosahexaenoic acid; Eosinophils; Peroxisome proliferator-activated receptor
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [17790666, 21790934]
- Grants-in-Aid for Scientific Research [21790934, 17790666] Funding Source: KAKEN
Background: Despite the fact that previous studies have indicated the significant roles of polyunsaturated fatty acids (PUFAs) in the immune system through peroxisome proliferator-activated receptor alpha (PPAR alpha) and PPAR gamma, the biological functions and the mechanisms of action in eosinophils are poorly understood. Methods: We investigated the functional effects of docosahexaenoic acid (DHA, n-3 PUFA) on human peripheral blood eosinophils, using in vitro systems to test the hypothesis that DHA negatively regulates eosinophil mechanisms through PPAR alpha and PPAR gamma. Results: Eosinophil apoptosis that spontaneously occurs under normal culture conditions was accelerated in the presence of DHA. In addition, eotaxin-directed eosinophil chemotactic responses were inhibited by pretreatment with DHA, disturbing both the velocity and the directionality of the cell movement. Pharmacological manipulations with specific antagonists indicated that the effects of DHA were not mediated through PPAR alpha and PPAR gamma, despite the presence of these nuclear receptors. DHA also induced Fas receptor expression and caspase-3 activation that appears to be associated with a proapoptotic effect of DHA. Further, DHA rapidly inhibited the expression of eotaxin receptor C-C chemokine receptor 3 and eotaxin-induced calcium influx and phosphorylation of extracellular signal-regulated kinase. Interestingly, these inhibitory effects were not observed with linoleic acid (n-6 PUFA). Conclusions: The data might explain one of the mechanisms found in previous research showing the favorable effects of n-3 PUFA supplementation on allergic diseases, and provide novel therapeutic strategies to treat eosinophilic disorders. Copyright (C) 2012 S. Karger AG, Basel
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