Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation.[5] TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors on other cells.[6] It is a member of the tumor necrosis factor superfamily, a family of transmembrane proteins that are cytokines, chemical messengers of the immune system.[7] Excessive production of TNF plays a critical role in several inflammatory diseases, and TNF-blocking drugs are often employed to treat these diseases.[8]
TNF is produced primarily by macrophages but is also produced in several other cell types, such as T cells, B cells, dendritic cells, and mast cells. It is produced rapidly in response to pathogens, cytokines, and environmental stressors.[9] TNF is initially produced as a type II transmembrane protein (tmTNF), which is then cleaved by TNF alpha converting enzyme (TACE) into a soluble form (sTNF) and secreted from the cell.[10] Three TNF molecules assemble together to form an active homotrimer, whereas individual TNF molecules are inert.[10]
When TNF binds to its receptors, tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2), a pathway of signals is triggered within the target cell, resulting in an inflammatory response. sTNF can only activate TNFR1, whereas tmTNF can activate both TNFR1 and TNFR2,[6] as well as trigger inflammatory signaling pathways within its own cell.[11] TNF's effects on the immune system include the activation of white blood cells, blood coagulation, secretion of cytokines, and fever.[5] TNF also contributes to homeostasis in the central nervous system.[12]
Inflammatory diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease can be effectively treated by drugs that inhibit TNF from binding to its receptors.[8] TNF is also implicated in the pathology of other diseases including cancer, liver fibrosis, and Alzheimer's, although TNF inhibition has yet to show definitive benefits.[13]
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