Mencin A, Kluwe J, Schwabe R F
Columbia University, College of Physicians and Surgeons, New York, NY, USA.
Gut. 2009 May;58(5):704-20. doi: 10.1136/gut.2008.156307.
Toll-like receptors (TLRs) recognise pathogen-associated molecular patterns (PAMPs) to detect the presence of pathogens. In addition to their role in innate immunity, TLRs also play a major role in the regulation of inflammation, even under sterile conditions such as injury and wound healing. This involvement has been suggested to depend, at least in part, on the ability of TLRs to recognise several endogenous TLR ligands termed damage-associated molecular patterns (DAMPs). The liver not only represents a major target of bacterial PAMPs in many disease states but also upregulates several DAMPs following injury. Accordingly, TLR-mediated signals have been implicated in a number of chronic liver diseases. Here, we will summarise recent findings on the role TLRs and TLR ligands in the pathophysiology of liver fibrosis and cirrhosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease and hepatocellular carcinoma, and highlight the potential role of TLR agonists, antagonists and probiotics for the treatment of chronic liver disease.
Toll样受体(TLRs)识别病原体相关分子模式(PAMPs)以检测病原体的存在。除了在先天免疫中的作用外,TLRs在炎症调节中也起主要作用,即使在诸如损伤和伤口愈合等无菌条件下也是如此。这种参与至少部分地被认为取决于TLRs识别几种称为损伤相关分子模式(DAMPs)的内源性TLR配体的能力。肝脏不仅在许多疾病状态下是细菌PAMPs的主要靶标,而且在损伤后会上调几种DAMPs。因此,TLR介导的信号与多种慢性肝病有关。在这里,我们将总结关于TLRs和TLR配体在肝纤维化和肝硬化、病毒性肝炎、酒精性肝病、非酒精性脂肪性肝病和肝细胞癌病理生理学中的作用的最新发现,并强调TLR激动剂、拮抗剂和益生菌在慢性肝病治疗中的潜在作用。