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首页> 外文期刊>American Journal of Physiology >Polyamines are required for expression of Toll-like receptor 2 modulating intestinal epithelial barrier integrity.
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Polyamines are required for expression of Toll-like receptor 2 modulating intestinal epithelial barrier integrity.

机译：多胺是表达Toll样受体2调节肠上皮屏障完整性所必需的。

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摘要

The Toll-like receptors (TLRs) allow mammalian intestinal epithelium to detect various microbes and activate innate immunity after infection. TLR2 and TLR4 have been identified in intestinal epithelial cells (IECs) as fundamental components of the innate immune response to bacterial pathogens, but the exact mechanism involved in control of TLR expression remains unclear. Polyamines are implicated in a wide variety of biological functions, and regulation of cellular polyamines is a central convergence point for the multiple signaling pathways driving different epithelial cell functions. The current study determined whether polyamines regulate TLR expression, thereby modulating intestinal epithelial barrier function. Depletion of cellular polyamines by inhibiting ornithine decarboxylase (ODC) with alpha-difluoromethylornithine decreased levels of TLR2 mRNA and protein, whereas increased polyamines by ectopic overexpression of the ODC gene enhanced TLR2 expression. Neither intervention changed basal levels of TLR4. Exposure of normal IECs to low-dose (5 microg/ml) LPS increased ODC enzyme activity and stimulated expression of TLR2 but not TLR4, while polyamine depletion prevented this LPS-induced TLR2 expression. Decreased TLR2 in polyamine-deficient cells was associated with epithelial barrier dysfunction. In contrast, increased TLR2 by the low dose of LPS enhanced epithelial barrier function, which was abolished by inhibition of TLR2 expression with specific, small interfering RNA. These results indicate that polyamines are necessary for TLR2 expression and that polyamine-induced TLR2 activation plays an important role in regulating epithelial barrier function.
机译：Toll样受体（TLR）使哺乳动物的肠上皮能够检测各种微生物并在感染后激活先天免疫。 TLR2和TLR4已在肠道上皮细胞（IEC）中鉴定为对细菌病原体的先天免疫应答的基本组成部分，但尚不清楚控制TLR表达的确切机制。多胺与多种生物学功能有关，细胞多胺的调节是驱动不同上皮细胞功能的多种信号通路的中心收敛点。当前的研究确定多胺是否调节TLR表达，从而调节肠上皮屏障功能。通过用α-二氟甲基鸟氨酸抑制鸟氨酸脱羧酶（ODC）消耗细胞多胺可降低TLR2 mRNA和蛋白质的水平，而通过ODC基因异位过表达而增加的多胺可增强TLR2的表达。两种干预均未改变TLR4的基础水平。正常IECs暴露于低剂量（5 microg / ml）LPS会增加ODC酶的活性并刺激TLR2的表达，但不会刺激TLR4的表达，而多胺的消耗阻止了LPS诱导的TLR2的表达。多胺缺陷细胞中TLR2的减少与上皮屏障功能障碍有关。相反，低剂量的LPS会增加TLR2，从而增强上皮屏障功能，而特异的小干扰RNA会抑制TLR2的表达，从而消除上皮屏障功能。这些结果表明，多胺对于TLR2表达是必需的，并且多胺诱导的TLR2活化在调节上皮屏障功能中起重要作用。

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