Tumor necrosis factor-α signaling in macrophages.
Tumor necrosis factor-α signaling in macrophages.
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DOI：
10.1615/critreveukargeneexpr.v20.i2.10
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发表时间：
2010
影响因子：
1.6
通讯作者：
Patial S
中科院分区：
文献类型：
--
作者：
Parameswaran N;Patial S
肿瘤坏死因子α在20多年前被克隆，并在一定程度上导致了肿瘤坏死因子及其受体超家族的发现。肿瘤坏死因子α通过两种跨膜受体，即肿瘤坏死因子受体1和肿瘤坏死因子受体2进行信号转导，调节细胞的增殖、存活、分化和凋亡等一系列重要功能。巨噬细胞是产生肿瘤坏死因子α的主要来源，有趣的是，巨噬细胞也对肿瘤坏死因子α高度敏感。肿瘤坏死因子α的异常产生和肿瘤坏死因子受体信号与多种疾病的发生有关，包括类风湿性关节炎、克罗恩病、动脉粥样硬化、银屑病、败血症、糖尿病和肥胖。肿瘤坏死因子α已被证明在许多炎症性疾病的细胞因子级联反应中起着关键作用，并且由于其作为炎性细胞因子产生的“主调节器”的作用，它已被提议作为许多疾病的治疗靶点。事实上，抗肿瘤坏死因子α药物现在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。本文就肿瘤坏死因子α的发现及其在调节巨噬细胞生物学中的作用作一综述。鉴于它在几种人类疾病中的重要性，我们还简要讨论了抗肿瘤坏死因子α疗法在炎症性疾病治疗中的作用。
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.
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