Parameswaran Narayanan, Patial Sonika
Department of Physiology and Division of Pathology, Michigan State University, East Lansing, MI 48824, USA.
Crit Rev Eukaryot Gene Expr. 2010;20(2):87-103. doi: 10.1615/critreveukargeneexpr.v20.i2.10.
Tumor necrosis factor-α (TNFα) was cloned over 2 decades ago and its identification in part led to the discovery of a super family of tumor necrosis factors (TNFs) and their receptors. TNFα signals through two transmembrane receptors, TNFR1 and TNFR2, and regulates a number of critical cell functions including cell proliferation, survival, differentiation, and apoptosis. Macrophages are the major producers of TNFα and interestingly are also highly responsive to TNFα. Aberrant TNFα production and TNF receptor signaling have been associated with the pathogenesis of several diseases, including rheumatoid arthritis, Crohn's disease, atherosclerosis, psoriasis, sepsis, diabetes, and obesity. TNFα has been shown to play a pivotal role in orchestrating the cytokine cascade in many inflammatory diseases and because of this role as a "master-regulator" of inflammatory cytokine production, it has been proposed as a therapeutic target for a number of diseases. Indeed anti-TNFα drugs are now licensed for treating certain inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. In this review we discuss the discovery of TNFα and its actions especially in regulating macrophage biology. Given its importance in several human diseases, we also briefly discuss the role of anti-TNFα therapeutics in the treatment of inflammatory diseases.
肿瘤坏死因子-α（TNFα）在20多年前就被克隆出来了，它的发现部分促成了肿瘤坏死因子（TNFs）及其受体超家族的发现。TNFα通过两种跨膜受体TNFR1和TNFR2发出信号，并调节许多关键的细胞功能，包括细胞增殖、存活、分化和凋亡。巨噬细胞是TNFα的主要产生者，有趣的是，它们对TNFα也高度敏感。TNFα的异常产生和TNF受体信号传导与多种疾病的发病机制有关，包括类风湿性关节炎、克罗恩病、动脉粥样硬化、牛皮癣、败血症、糖尿病和肥胖症。在许多炎症性疾病中，TNFα已被证明在协调细胞因子级联反应中起关键作用，并且由于它作为炎症细胞因子产生的“主调节器”这一作用，它已被提议作为多种疾病的治疗靶点。事实上，抗TNFα药物现已被批准用于治疗某些炎症性疾病，包括类风湿性关节炎和炎症性肠病。在这篇综述中，我们讨论了TNFα的发现及其作用，特别是在调节巨噬细胞生物学方面的作用。鉴于其在几种人类疾病中的重要性，我们还简要讨论了抗TNFα疗法在炎症性疾病治疗中的作用。
