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

Modulation of hepatic PPAR expression during Ft LVS LPS-induced protection from Francisella tularensis LVS infection.
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DOI:
10.1186/1471-2334-10-10
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发表时间:
2010-01-18
影响因子:
3.7
通讯作者:
Crasta OR
Crasta OR
中科院分区:
医学3区
文献类型:
--
作者:
Mohapatra SK;Cole LE;Evans C;Sobral BW;Bassaganya-Riera J;Hontecillas R;Vogel SN;Crasta OR

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先前的研究表明,土拉弗朗西斯菌(Ft)活疫苗株(LVS)脂多糖(LPS)可以保护小鼠免受Ft LVS的后续攻击,并减弱促炎细胞因子的反应。为了进一步研究Ft - LVS LPS介导的保护作用的分子机制,我们使用Affymetrix阵列分析了Ft - LVS LPS或生理盐水预处理和随后Ft - LVS刺激后的肝脏基因表达。感染后48小时,大量基因(约3000个)出现差异表达。在存活小鼠中,用Ft LVS LPS预处理后,炎症基因受感染的调节程度明显减弱。然而,Ft LVS LPS单独对未感染小鼠的基因表达谱有微妙的影响。通过基因集富集分析,我们发现由过氧化物酶体增殖物激活受体(PPARs)调控的脂肪酸代谢途径显著上调。我们假设lps诱导的小鼠促炎反应减弱部分是由PPARs (α和γ)介导的。
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. 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. 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). We hypothesize that the LPS-induced blunting of pro-inflammatory response in mouse is, in part, mediated by PPARs (α and γ).
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