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

Biochim Biophys Acta. 2011 Sep;1812(9):1164-9. doi: 10.1016/j.bbadis.2011.05.002. Epub 2011 May 17.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Asthma / prevention & control*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Caenorhabditis elegans Proteins / biosynthesis
  • Caenorhabditis elegans Proteins / genetics*
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Docosahexaenoic Acids / metabolism
  • Eicosapentaenoic Acid / analogs & derivatives
  • Eicosapentaenoic Acid / metabolism
  • Fatty Acid Desaturases / biosynthesis
  • Fatty Acid Desaturases / genetics*
  • Fatty Acids, Omega-3 / metabolism*
  • Female
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Respiratory Hypersensitivity / prevention & control


  • Caenorhabditis elegans Proteins
  • Chemokines
  • Cytokines
  • Fatty Acids, Omega-3
  • fat-1 protein, C elegans
  • protectin D1
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Fatty Acid Desaturases
  • 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid