期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1812, 期 9, 页码 1164-1169出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2011.05.002
关键词
Omega-3; Resolvins; Protectins; Inflammation; Asthma; Fat-1 mice
资金
- NIH [NIH R01 113605, AI068084]
- Boehringer Ingelheim Fonds
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 El, 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-1 alpha, 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 El 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. (C) 2011 Elsevier B.V. All rights reserved.
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