Expression data from mouse liver infected with Ft LVS (without or with LPS pretreatment)
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ABSTRACT: 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).
Project description: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). Experiment 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.
Project description:These microarray studies are part of a larger study characterizing a deletion mutant of the putative transcriptional regulator IclR in Francisella tularensis LVS and SchuS4 strains. The microarrays were performed using RNA isolated from wild-type LVS and a LVS iclR deletion mutant after growing in Chamberlain?s defined media pH 6.3 to early mid-log phase. Results suggest that IclR affects expression of several genes after determining statistically significant differences by SAM.
Project description:Transcriptional profiling of LVS grown in hepatocytic cell line FL83B was compared to that of LVS cultued in MH broth to discover genes important for intracellular growth.
Project description:These microarray studies are part of a larger study characterizing a deletion mutant of the putative transcriptional regulator IclR in Francisella tularensis LVS and SchuS4 strains. The microarrays were performed using RNA isolated from wild-type LVS and a LVS iclR deletion mutant after growing in Chamberlain?s defined media pH 6.3 to early mid-log phase. Results suggest that IclR affects expression of several genes after determining statistically significant differences by SAM. Comparison of gene expression between LVS iclR deletion mutant vs. wild-type LVS.
Project description:Gene expression profiling reveals anti-inflammatory effects of BTEE on lipopolysaccharide (LPS)-induced murine RAW264 cells We evaluated the pretreatment effect of BTEE on LPS-induced inflammation in RAW264 cells. Pretreatment with BTEE could significantly attenuate nitric oxide (NO) production and LPS-induced release of inflammatory mediators in RAW264 cells.