在弗氏李斯特菌 LVS LPS 诱导的对抗弗朗西斯菌 tularensis LVS 感染的保护作用期间，肝脏 PPAR 表达的调节。

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

机构信息

Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

出版信息

BMC Infect Dis. 2010 Jan 18;10:10. doi: 10.1186/1471-2334-10-10.

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).

背景

先前的研究表明，弗氏柠檬酸杆菌活疫苗株（Ft）脂多糖（LPS）的给药可保护小鼠免受后续 Ft LVS 挑战，并减轻促炎细胞因子反应。

方法

为了进一步研究 Ft LVS LPS 介导保护的分子机制，我们使用 Affymetrix 阵列分析了 Ft LVS LPS 或生理盐水预处理以及随后 Ft LVS 挑战后 48 小时内的全肝基因表达谱。

结果

感染后 48 小时，大量基因（>3000 个）表达差异。在幸存小鼠中，Ft LVS LPS 预处理明显减弱了感染引起的炎症基因的调节程度。然而，Ft LVS LPS 单独对未感染小鼠的基因表达谱几乎没有影响。通过基因集富集分析，我们发现脂肪酸代谢途径显著上调，该途径受过氧化物酶体增殖物激活受体（PPARs）调节。