Fat-1 transgenic mice with elevated omega-3 fatty acids are protected from allergic airway responses

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1812

Article

Bilal, Sueleyman^1,2,5  Haworth, Oliver^3,4  Wu, Lijun⁶  Weylandt, Karsten H.^1,2,5  Levy, Bruce D.^3,4  Kang, Jing X.^1,2 

[1] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA 02114 USA

[3] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

[5] Charite, Dept Gastroenterol, D-13353 Berlin, Germany

[6] Resolvyx Pharmaceut Inc, Bedford, MA 01730 USA

关键词: Omega-3;    Resolvins;    Protectins;    Inflammation;    Asthma;    Fat-1 mice;   

DOI  :  10.1016/j.bbadis.2011.05.002

来源: Elsevier

【 摘 要 】

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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