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

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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.

Research highlights

► Fat-1 mice had increased endogenous lung omega-3 polyunsaturated fatty acids. ► These mice showed decreased allergen-induced airway inflammation. ► This was associated with alleviated methacholine-induced bronchoconstriction. ► Lavage fluid concentrations of IL-1α, IL-2, IL-5, IL-9, IL-13, G-CSF, KC and RANTES were decreased. ► Anti-inflammatory protectin D1 and resolvin E1 were increased in fat-1 lungs.

Keywords

Omega-3
Resolvins
Protectins
Inflammation
Asthma
Fat-1 mice

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These authors contributed equally to this study.