PPARbeta/delta protects against experimental colitis through a ligand-independent mechanism.
PPARbeta/delta protects against experimental colitis through a ligand-independent mechanism.
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发表时间：
2007
影响因子：
3.1
通讯作者：
Holly E. Hollingshead;K. Morimura;M. Adachi;Mary J. Kennett;A. Billin;T. Willson;F. Gonzalez;J. Peters
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文献类型：
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作者：
Holly E. Hollingshead;K. Morimura;M. Adachi;Mary J. Kennett;A. Billin;T. Willson;F. Gonzalez;J. Peters
过氧化物酶体增殖物激活受体（PPARs）β/δ和γ在炎症反应基因的负调控中具有重叠作用。PPARgamma的配体活化保护小鼠免受实验性结肠炎。PPARbeta/delta可以负调节炎症，并且在结肠的上皮细胞中高度表达，因此PPARbeta/delta也可能在实验性结肠炎中起作用。在这些研究中，在野生型和PPARbeta/delta缺失小鼠中，通过葡聚糖硫酸钠（DSS）处理诱导结肠炎，有和没有PPARbeta/delta特异性配体GW 0742。PPARbeta/delta-null小鼠表现出对DSS诱导的结肠炎的敏感性增加，如与类似治疗的野生型小鼠相比，体重减轻、结肠长度、结肠形态、髓过氧化物酶活性和编码炎性标志物干扰素γ、肿瘤坏死因子-α和白细胞介素-6的mRNA表达增加的显著差异所示。有趣的是，这些差异不受任何基因型中的PPARbeta/delta的配体活化的影响。这些研究表明，PPARbeta/delta在结肠上皮中的表达通过配体非依赖性机制抑制炎症并保护免受DSS诱导的结肠炎。
Peroxisome proliferator-activated receptors (PPARs) beta/delta and gamma have overlapping roles in the negative regulation of inflammatory response genes. Ligand activation of PPARgamma protects against experimental colitis in mice. PPARbeta/delta can negatively regulate inflammation and is highly expressed in the epithelial cells of the colon, therefore PPARbeta/delta may also have a role in experimental colitis. In these studies, colitis was induced by dextran sodium sulfate (DSS) treatment in wild-type and PPARbeta/delta-null mice, with and without the PPARbeta/delta specific ligand GW0742. PPARbeta/delta-null mice exhibited increased sensitivity to DSS-induced colitis, as shown by marked differences in body weight loss, colon length, colonic morphology, myeloperoxidase activity and increased expression of mRNAs encoding the inflammatory markers interferon gamma, tumor necrosis factor-alpha, and interleukin-6 compared to similarly treated wild-type mice. Interestingly, these differences were not affected by ligand activation of PPARbeta/delta in either genotype. These studies demonstrate that PPARbeta/delta expression in the colonic epithelium inhibits inflammation and protects against DSS-induced colitis through a ligand-independent mechanism.