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lüll Tumor necrosis factor-alpha signaling in macrophages Parameswaran N; Patial SCrit Rev Eukaryot Gene Expr 2010[]; 20 (2): 87-103Tumor necrosis factor-alpha (TNFalpha) 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. TNFalpha 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 TNFalpha and interestingly are also highly responsive to TNFalpha. Aberrant TNFalpha 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. TNFalpha 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-TNFalpha drugs are now licensed for treating certain inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. In this review we discuss the discovery of TNFalpha and its actions especially in regulating macrophage biology. Given its importance in several human diseases, we also briefly discuss the role of anti-TNFalpha therapeutics in the treatment of inflammatory diseases.|Animals[MESH]|Arthritis/metabolism[MESH]|Humans[MESH]|Inflammation/metabolism[MESH]|Inflammatory Bowel Diseases/metabolism[MESH]|Macrophages/*metabolism[MESH]|Signal Transduction/*physiology[MESH]|Tumor Necrosis Factor-alpha/*physiology[MESH] |