Modulation of hepatic PPAR expression during Ft LVS LPS-induced protection from Francisella tularensis LVS infection

Abstract

BackgroundIt 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.MethodsTo 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.ResultsA 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).ConclusionsWe hypothesize that the LPS-induced blunting of pro-inflammatory response in mouse is, in part, mediated by PPARs (α and γ).

When Pictures Waste a Thousand Words: Analysis of the 2009 H1N1 Pandemic on Television News

“…In addition, public health agencies identified priority groups, which is a common tool in the arsenal of public health agencies for interventions like vaccination during a pandemic. Other studies have found that advertising priority groups reinforces behaviour change and health behaviours including vaccination [29] among priority group members. However, it also decreases the risk perception of individuals not identified as priority groups [29].…”

“…Other studies have found that advertising priority groups reinforces behaviour change and health behaviours including vaccination [29] among priority group members. However, it also decreases the risk perception of individuals not identified as priority groups [29].…”

Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity

“…We and others have shown previously that antibodies to this endogenous LPS are produced, making up the majority of the anti-F. tularensis IgM response and a small fraction of the IgG response in LVS-V-immunized mice (25,(41)(42)(43). However, F. tularensis LPS-mediated protection is effective only in a narrow 2-day window prior to challenge and does not yield lasting protection against systemic or aerosol challenge, although partial protection against intradermal challenge and low-virulence strains was observed in previous studies (13,(41)(42)(43)(44)(45). Inclusion of synthetic MPL in the LVS-V vaccine augmented IgG titers significantly (Fig.…”

The Synthetic Cannabinoid R(+)WIN55,212-2 Augments Interferon-β Expression via Peroxisome Proliferator-activated Receptor-α

“…Indeed, the ability of R(ϩ)WIN55,212-2 to up-regulate the expression of PPAR␣ adds to previous studies describing a similar effect of this aminoalkylindole on PPAR␥ expression (58,59), suggesting that the impact of R(ϩ)WIN55,212-2 on proliferative and inflammatory pathways may be due to its effects on PPAR expression. It is also noteworthy that LPS can enhance PPAR␣ expression (76), and evidence from our group suggests that endogenous PPAR␣ expression is up-regulated in EAE spinal cord and in peripheral blood mononuclear cells isolated from MS patients (data not shown). Further experiments will determine if this represents an endogenous neuroprotective response, an attractive possibility given that an up-regulation in PPAR expression has been shown to inhibit proinflammatory signaling (77).…”