Mechanisms of gut barrier failure in the pathogenesis of necrotizing enterocolitis: Toll-like receptors throw the switch.
Mechanisms of gut barrier failure in the pathogenesis of necrotizing enterocolitis: Toll-like receptors throw the switch.
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DOI：
10.1053/j.sempedsurg.2013.01.003
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发表时间：
2013-05
影响因子：
1.7
通讯作者：
Sodhi CP
中科院分区：
文献类型：
--
作者：
Hackam DJ;Good M;Sodhi CP
坏死性小肠结肠炎(NEC)是导致早产儿胃肠道原因死亡的主要原因，在过去的三十年里，它的总体存活率并没有提高。虽然NEC的确切病因仍不完全清楚，但我们和其他人已经表明，NEC发展和繁殖的一个主要易感因素是肠道屏障的破坏，导致细菌易位和全身性败血症。在寻求确定相关原因的过程中，我们和其他人还确定，细菌内毒素受体，即Toll样受体4(TLR4)的激活，是导致NEC的肠屏障衰竭发展所必需的。我们还表明，早产儿被赋予了一些策略，这些策略可以限制或促进肠道内TLR4信号的程度，这些策略共同决定了NEC发育的相对倾向。在这篇综述中，我们将通过对TLR4信号在肠屏障衰竭中的作用的调查，来强调TLR4信号在NEC发病机制中的证据。我们将确定肠道内TLR4调节如何解释早产儿对NEC发展的独特易感性，并将强调限制TLR4信号转导程度的策略如何作为这种毁灭性疾病的新治疗方法。
Necrotizing enterocolitis (NEC) is the leading cause of death from gastro-intestinal causes in premature infants, and its overall survival has not improved in the past three decades. While the precise cause of NEC remains incompletely understood, we and others have shown that a major predisposing factor in the development and propagation of NEC is a breakdown of the intestinal barrier which leads to bacterial translocation and systemic sepsis. In seeking to identify the causes involved, we and others have also determined that activation of the receptor for bacterial endotoxin, namely toll like receptor 4 (TLR4), is required for the development of intestinal barrier failure leading to NEC. We have also shown that the premature infant is endowed with strategies that can either limit or promote the extent of TLR4 signaling within the gut, which together determine the relative propensity with which NEC develops. In this review, we will highlight the evidence for TLR4 signaling in the pathogenesis of NEC through a survey of its effects on gut barrier failure. We will identify how TLR4 regulation within the gut can explain the unique susceptibility of the premature infant to the development of NEC, and will highlight how strategies to limit the degree of TLR4 signaling can serve as novel therapeutic approaches for this devastating disease.
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DOI：
10.4049/jimmunol.1103114
发表时间：
2012-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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影响因子：
3.6
作者：
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DOI：
10.1152/ajpgi.00328.2004
发表时间：
2005-05-01
影响因子：
4.5
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1136/archdischild-2011-300435
发表时间：
2013-01-01
影响因子：
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作者：
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通讯作者：
Leticia Echaniz-Aviles, Maria Olga