Tumor necrosis factor
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]
- ^ a b c ENSG00000230108, ENSG00000223952, ENSG00000204490, ENSG00000228321, ENSG00000232810, ENSG00000228849, ENSG00000206439 GRCh38: Ensembl release 89: ENSG00000228978, ENSG00000230108, ENSG00000223952, ENSG00000204490, ENSG00000228321, ENSG00000232810, ENSG00000228849, ENSG00000206439 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024401 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Cite error: The named reference
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DeathByInflammationwas invoked but never defined (see the help page). - ^ Croft M, Siegel RM (March 2017). "Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases". Nature Reviews Rheumatology. 13 (4): 217–233. doi:10.1038/nrrheum.2017.22. PMC 5486401. PMID 28275260.
- ^ a b Cite error: The named reference
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TNFOnCNSwas invoked but never defined (see the help page). - ^ Sethi JK, Hotamisligil GS (October 2021). "Metabolic Messengers: tumour necrosis factor". Nature Metabolism. 3 (10): 1302–1312. doi:10.1038/s42255-021-00470-z. PMID 34650277.