A lipidomics analysis of influenza infection and PPAR g activation

While vaccines are a reliable preventative of influenza infection, useful therapeutics for treatment of the disease would be key to minimizing the impact of a major pandemic. In this study we have focused on the use of the anti-inflammatory compounds Abscisic Acid (ABA) and NSC61610 (NSC) in the presence of PPARγ to reduce lung inflammation and damage. The mechanisms by which these therapeutics activate PPARγ have not yet been identified, but a promising avenue is through the modification of known lipid mediators produced during Arachidonic Acid metabolism. In this study, we present a lipidomics analysis of influenza infected C57BL6 Wild Type mice treated with ABA and NSC. Our data demonstrate a rise in lipid mediator levels due to infection as well as in the presence of ABA, and to a lesser extent, NSC. Quantitative Real-Time PCR was performed in order to link the expression of lipid metabolic regulators to observed changes in lipid levels. In addition to this, molecular docking studies of PPARγ were performed to compare predicted binding affinities of previously identified ligands to other eicosanoids. The results of the simulations rank many previously identified PPARγ ligands below other metabolites, indicating that studies analyzing for the presence of previously unexplored eicosanoids may be fruitful in identifying new lipid mediators involved in anti- inflammatory pathways.