Membrane TLR signaling mechanisms in the gastrointestinal tract during sepsis.
Membrane TLR signaling mechanisms in the gastrointestinal tract during sepsis.
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DOI：
10.1111/j.1365-2982.2009.01464.x
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发表时间：
2010-03
影响因子：
3.5
通讯作者：
Bauer AJ
中科院分区：
文献类型：
--
作者：
Buchholz BM;Bauer AJ
我们的细菌居民是致命的两面神，可以导致败血症诱导的全身炎症反应综合征和多器官衰竭。超过一半的ICU患者患有感染，败血症仍然是美国十大死亡原因之一。严重肠梗阻经常伴随脓毒症，建立了一个肠道源性微生物移位和肠道产生大量强效全身炎症介质的阴险循环。在预防/治疗脓毒症后遗症方面，几乎没有治疗进展。本文就细胞膜Toll样受体（TLR）在肠梗阻发病中的作用机制作一综述。几乎没有关于肠梗阻的革兰氏阳性/TLR 2信号传导机制的数据，然而，TLR 2可以被许多炎症介质高度诱导，并且需要使用革兰氏阳性脓毒症的临床相关情况进行研究。特定的革兰氏阴性/TLR 4信号传导途径正在使用“逆向工程”方法阐明，并且已经揭示内毒素诱导的肠梗阻由经典白细胞炎症信号传导和MyD 88依赖性非骨髓衍生机制双重介导，但是单个细胞群体的特定作用仍然未知。与TLR 2一样，鞭毛蛋白/TLR 5信号传导在肠梗阻中的作用也知之甚少。但是，通过了解其他系统中的TLR信号可以学到很多东西。显然，多微生物模型的使用提供了重要的临床相关性，但几乎所有模式识别受体的同时激活使得不可能离散地研究特定的信号通路。我们相信，对单个TLR通路的解剖，然后可以以有意义的方式智能地重新组装，将为脓毒症诱导的肠梗阻的治疗提供见解。
Our bacterial residents are deadly Janus-faced indwellers which can lead to a septic-induced systemic inflammatory response syndrome and multiple organ failure. Over half of ICU patients suffer from infections and sepsis remains among the top ten causes of death in the United States. Severe ileus frequently accompanies sepsis setting up an insidious cycle of gut-derived microbial translocation and the copious intestinal production of potent systemic inflammatory mediators. Few therapeutic advances have occurred to prevent/treat the sequelae of sepsis. Here, we selectively review studies on cellular membrane bound Toll-like receptor (TLR) mechanisms of ileus. Virtually no data exists on Gram-positive/TLR2 signaling mechanisms of ileus, however, TLR2 is highly inducible by numerous inflammatory mediators and studies using clinically relevant scenarios of Gram-positive sepsis are needed. Specific Gram-negative/TLR4 signaling pathways are being elucidated using a “reverse engineering” approach and have revealed that endotoxin induced ileus is dually mediated by classical leukocyte inflammatory signaling and by a MyD88-dependent non-bone marrow derived mechanism, but the specific roles of individual cell populations are still unknown. Like TLR2, little is also know of the role of flagellin/TLR5 signaling in ileus. But, much can be learned by understanding TLR signaling in other systems. Clearly, the use of polymicrobial models provide important clinical relevancy but simultaneous activation of virtually all pattern recognition receptors make it impossible to discretely study specific signaling pathways. We believe that dissection of individual TLR pathways, which can then be intelligently re-assembled in a meaningful manner, will provide insight into treatments for sepsis induced ileus.
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影响因子：
3.8
作者：
Deitch, EA
通讯作者：
Deitch, EA
DOI：
10.1152/ajpgi.00545.2006
发表时间：
2007-07-01
影响因子：
4.5
作者：
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影响因子：
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作者：
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通讯作者：
Kalff, Jorg C
DOI：
10.1073/pnas.92.22.10359
发表时间：
1995-10-24
影响因子：
11.1
作者：
DEKIMPE, SJ;KENGATHARAN, M;VANE, JR
通讯作者：
VANE, JR