Implication of Toll-like receptor and tumor necrosis factor α signaling in septic shock
Implication of Toll-like receptor and tumor necrosis factor α signaling in septic shock
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DOI：
10.1097/01.shk.0000180074.69143.77
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发表时间：
2005-09-01
期刊：
影响因子：
3.1
通讯作者：
Yeh, WC
中科院分区：
文献类型：
--
作者：
Lin, WJ;Yeh, WC
感染性休克是由对微生物感染的全身炎症反应引发的，其经常导致灌注受损和多器官衰竭。由于其高死亡风险，感染性休克是一个主要问题，特别是对重症监护病房的患者。通常，细菌脂多糖（LPS）是各种免疫应答的强激活剂，并刺激单核细胞/巨噬细胞释放各种炎性细胞因子。然而，已知响应于细菌感染的炎性因子的过度产生会引起败血性休克，类似于由LPS诱导的败血性休克。LPS信号通路和下游炎症细胞因子的研究可能对脓毒症的治疗具有重要意义。近年来，在理解由LPS及其受体Toll样受体4（TLR 4）以及由肿瘤坏死因子α（TNF α）（LPS刺激诱导的强效炎性细胞因子）激活的信号通路方面取得了显著进展。本文简要总结了我们目前的知识，这些信号通路和关键的信号转导。关键信号转导的表征可能使我们能够识别易于处理的脓毒症治疗干预的新靶点。
Septic shock is initiated by a systemic inflammatory response to microbial infection that frequently leads to impaired perfusion and multiple organ failure. Because of its high risk of death, septic shock is a major problem particularly for patients in the intensive care unit. In general, bacterial lipopolysaccharide (LPS) is a strong activator of various immune responses and stimulates monocytes/macrophages to release a variety of inflammatory cytokines. However, overproduction of inflammatory factors in response to bacterial infections is known to cause septic shock, similar to that induced by LPS. Studies of LPS-signaling pathways and downstream inflammatory cytokines may have critical implications in the treatment of sepsis. In recent years, there has been significant progress in understanding the signaling pathways activated by LPS and its receptor Toll-like receptor 4 (TLR4), as well as by tumor necrosis factor alpha (TNF alpha), a potent inflammatory cytokine induced by LPS stimulation. This review briefly summarizes our current knowledge of these signaling pathways and critical signal transducers. Characterization of key signal transducers may allow us to identify tractable, novel targets for the therapeutic interventions of sepsis.