Holtmann M H, Schütz M, Galle P R, Neurath M F
Department of Medicine, Johannes-Gutenberg-University, Mainz, Germany.
Z Gastroenterol. 2002 Aug;40(8):587-600. doi: 10.1055/s-2002-33418.
As a result of extensive clinical and basic research, the pivotal role of tumour necrosis factor (TNF) in the pathogenesis of chronic inflammatory diseases such as inflammatory bowel disease (IBD) has now generally been acknowledged. This has led to promising clinically effective anti-TNF-strategies. Of note, there is more and more evidence that TNF seems to play a key role in other gastrointestinal diseases including Helicobacter pylori infection, pancreatitis, viral hepatitis and toxic liver damage, too. The action of TNF at the cellular level is mediated by two cell surface receptors, TNF-R1 (p60) and TNF-R2 (p80). The function of these receptors and the downstream intracellular signal transduction pathway have been extensively studied in vitro and it can be expected, that there are critically important steps in TNF-signal transduction that might be dysregulated in these disease states. Their elucidation could lead to a better understanding of the pathogenesis of these diseases, in particular IBD and potentially reveal new, more specific therapeutic targets. Objective of this review is to give an overview about the current knowledge on TNF signal transduction in relationship to selected examples of important gastrointestinal disorders with special focus on IBD. Finally, the implications for future research efforts will be discussed.
经过广泛的临床和基础研究，肿瘤坏死因子（TNF）在诸如炎症性肠病（IBD）等慢性炎症性疾病发病机制中的关键作用现已得到普遍认可。这催生了颇具前景的临床有效抗TNF策略。值得注意的是，越来越多的证据表明，TNF似乎在包括幽门螺杆菌感染、胰腺炎、病毒性肝炎和中毒性肝损伤在内的其他胃肠道疾病中也发挥着关键作用。TNF在细胞水平的作用是由两种细胞表面受体介导的，即TNF-R1（p60）和TNF-R2（p80）。这些受体的功能以及下游细胞内信号转导途径已在体外得到广泛研究，可以预期，在这些疾病状态下，TNF信号转导中可能存在关键步骤失调的情况。对其进行阐明可能有助于更好地理解这些疾病的发病机制，尤其是IBD，并有可能揭示新的、更具特异性的治疗靶点。本综述的目的是概述目前关于TNF信号转导与重要胃肠道疾病的选定实例相关的知识，特别关注IBD。最后，将讨论对未来研究工作的启示。
