Expression data from mouse liver infected with Ft LVS (without or with LPS pretreatment). Mus musculus

Background: It has been shown previously that administration of Francisella tularensis (Ft) LVS lipopolysaccharide (LPS) protects mice against subsequent challenge with Ft LVS and blunts the pro-inflammatory cytokine response. Methods: To investigate further the molecular mechanisms that underlie Ft LVS LPS-mediated protection, we profiled global hepatic gene expression following Ft LVS LPS or saline pretreatment and subsequent Ft LVS challenge using Affymetrix arrays. Results: A large number of genes (> 3000) were differentially expressed at 48 hours post-infection. The degree of modulation of inflammatory genes by infection was clearly attenuated by LPS-pretreatment in the surviving mice. However, LPS alone had a subtle but significant effect on the gene expression profile of the uninfected mice. By employing gene set enrichment analysis, we discovered significant up-regulation of peroxisome proliferator activated receptors (PPARs) and their target genes in LPS-treated liver. Conclusions: We hypothesize that the LPS-induced blunting of pro-inflammatory response in mouse is, in part, mediated by PPARs (alpha and gamma). Overall design: Two groups of 9 mice each were used for this experiment. 48 hours prior to Ft LVS challenge, mice were injected i.p. with either 100 ng of Ft LVS LPS or an equivalent volume of saline. On the day of challenge, 3 saline- and 3 Ft LVS LPS-pretreated animals were sacrificed (uninfected controls), while all remaining mice were challenged i.p. with ~4-5 X 105 Ft LVS. Ft LVS-challenged mice were sacrificed (in groups of 3) at 24 and 48 hours post-infection.