Modulation of hepatic PPAR expression during Ft LVS LPS-induced protection from Francisella tularensis LVS infection.
BMC Infect Dis, 2010/1/18;10:10.
Mohapatra SK[1], Cole LE, Evans C, Sobral BW, Bassaganya-Riera J, Hontecillas R, Vogel SN, Crasta OR
Affiliations
PMID: 20082697DOI: 10.1186/1471-2334-10-10
Impact factor: 3.667
Abstract
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).
MeSH terms
Animals; Bacterial Vaccines; Fatty Acids; Female; Francisella tularensis; Gene Expression Profiling; Lipopolysaccharides; Liver; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Peroxisome Proliferator-Activated Receptors; Tularemia; Vaccines, Attenuated
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