Fat-1 transgenic mice with elevated omega-3 fatty acids are protected from allergic airway responses |
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Authors: | Sueleyman Bilal Oliver Haworth Lijun WuKarsten H Weylandt Bruce D Levy Jing X Kang |
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Institution: | a Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USAb Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA 02115, USAc Department of Gastroenterology, Virchow Campus, Charité University Medicine, Berlin, 13353, Germanyd Resolvyx Pharmaceuticals, Inc, Bedford, MA 01730, USA |
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Abstract: | Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been implicated in the alleviation of asthma. Recent studies have demonstrated that the n-3 PUFA derived lipid mediators, protectin D1 and resolvin E1, may act as potent resolution agonists in airway inflammation. The effects of the n-3 PUFA tissue status itself on asthma pathogenesis remains to be further investigated. In this study allergic airway inflammation induced by allergen sensitization and aerosol challenge in Fat-1 and wild-type mice was investigated. Fat-1 transgenic mice displayed increased endogenous lung n-3 PUFA. When allergen-sensitized and aerosol-challenged, these animals had decreased airway inflammation with decreased leukocyte accumulation in bronchoalveolar lavage fluid and lung parenchyma. The Fat-1 mice had a shift to the right in the dose-response relationship for methacholine induced bronchoconstriction with a significant increase in the log ED200. The Fat-1 mice had lower BALF concentrations of the pro-inflammatory cytokines IL-1α, IL-2, IL-5, IL-9, IL-13, G-CSF, KC and RANTES. Furthermore, increased lung tissue amounts of the counter-regulatory mediators protectin D1 and resolvin E1 were found in Fat-1 mice after bronchoprovocative challenge. These results therefore demonstrate a direct protective role for lung n-3 PUFA in allergic airway responses and an increased generation of protectin D1 and resolvin E1 in this context. |
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Keywords: | Omega-3 Resolvins Protectins Inflammation Asthma Fat-1 mice |
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