Modulation of hepatic PPAR expression during Ft LVS LPS-induced protection from Francisella tularensis LVS infection.
BACKGROUND
It has been shown previously that administration of Francisella tularensis (Ft) Live Vaccine Strain (LVS) lipopolysaccharide (LPS) protects mice against subsequent challenge with Ft LVS and blunts the pro-inflammatory cytokine response.


METHODS
To further investigate the molecular mechanisms that underlie Ft LVS LPS-mediated protection, we profiled global hepatic gene expression following Ft LVS LPS or saline pre-treatment and subsequent Ft LVS challenge using Affymetrix arrays.


RESULTS
A large number of genes (> 3,000) were differentially expressed at 48 hours post-infection. The degree of modulation of inflammatory genes by infection was clearly attenuated by pre-treatment with Ft LVS LPS in the surviving mice. However, Ft LVS LPS alone had a subtle effect on the gene expression profile of the uninfected mice. By employing gene set enrichment analysis, we discovered significant up-regulation of the fatty acid metabolism pathway, which is regulated by peroxisome proliferator activated receptors (PPARs).


CONCLUSIONS
We hypothesize that the LPS-induced blunting of pro-inflammatory response in mouse is, in part, mediated by PPARs (alpha and gamma).
Mohapatra
Saroj K
SK
Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. saroj@vt.edu
Cole
Leah E
LE
Evans
Clive
C
Sobral
Bruno W
BW
Bassaganya-Riera
Josep
J
Hontecillas
Raquel
R
Vogel
Stefanie N
SN
Crasta
Oswald R
OR
D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005604:Francisella tularensis; D020869:Gene Expression Profiling; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D014406:Tularemia / Q000235:genetics* / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology
D001428:Bacterial Vaccines; D005227:Fatty Acids; D008070:Lipopolysaccharides; D047492:Peroxisome Proliferator-Activated Receptors; D014613:Vaccines, Attenuated