Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6140418 | Virology | 2014 | 15 Pages |
Abstract
The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GXâ/â) model and found that survival after infection was significantly greater in GXâ/â mice than in GX+/+ mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GXâ/â mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GXâ/â mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.
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Virology
Authors
Alyson A. Kelvin, Norbert Degousee, David Banner, Eva Stefanski, Alberto J. LeÏn, Denis Angoulvant, Stéphane G. Paquette, Stephen S.H. Huang, Ali Danesh, Clinton S. Robbins, Hossein Noyan, Mansoor Husain, Gerard Lambeau, Michael Gelb, David J. Kelvin,