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

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.

• Authors: Sueleyman Bilal, Oliver Haworth, Lijun Wu, Karsten H Weylandt, Bruce D Levy, Jing X Kang
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1812 Issue 9 Pg. 1164-9 (Sep 2011) ISSN: 0006-3002 [Print] Netherlands
• PMID: 21616147 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• 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

Topics

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