TNF works through two receptors, TNFR1 and TNFR2. TNFR1 is the major signal receptor of TNF-α. TNFR2, which mediates limited biological responses, binds to TNF-α and TNF-β. TNF signaling transduction through TNFR1 and TNFR2 can induce a variety of cellular responses, which depends on many factors, including the metabolic state of the cell and the adaptor proteins present in the cell. These differences then affect the activation of many intracellular signaling pathways, including NF-κB, p38, JNK and ceramide/sphingomyelinase signaling pathway. The complexity of TNFR1-mediated signaling is the reason that allows many divergent outcomes to occur as a result of TNF signaling and contributes to the difficulties inherent with and the side effects resulting from broad TNF signaling inhibition. The major function of TNF signaling pathway is to regulate immune cells. It is able to induce fever, apoptotic cell death, cachexia, inflammation, and to inhibit tumorigenesis and virus replication, and respond to sepsis through cells that produce IL1 and IL6.
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