The prototypic ligand for the TNF superfamily is tumor necrosis factor alpha (TNF alpha, TNF alpha, TNFA), also called Cachectin or TNFSF2. It is a pleiotropic molecule that plays a key role in inflammation, immune system development and lipid metabolism. TNF-alpha can be produced by many lymphoid cells aswell as astrocytes and endothelial cells.
Mouse TNF-alpha antigen contains 35 amino acids (aa) cytoplasmic and 21 aa transmembrane segments, as well as a 179 (aa extracellular domain). The ECD contains mouse TNF alpha which shares 94% aa sequence identity to rat, and 70%-77% with bovine and cotton rat, canine and cotton rat, equine and feline, porcine and rhesus TNF alpha.
TNF-alpha can be produced by many immune, epithelial and endothelial cells. TNF-alpha is formed intracellularly to form noncovalently linked homotrimeric that are expressed on the cell's surface. TNF-alpha from cells can cause the lysis and infection of nearby tumor cells as well as virus infected cells. It can also generate downstream signaling by ligation with soluble TNFR 1.
TACE/ADAM17 can release the bioactive cytokine (a 55kDa molecular weight soluble trimmer from the TNF alpha extracellular domain) by shedding membrane-bound TNF-alpha. TNF-alpha binds to the ubiquitous 55-60kDa TNFRII and the hematopoietic-restricted80kDa TNFRIII. Both of these homotrimers are present on almost all cell types.
TNF-alpha is bound to both type I and II receptors with similar affinity. However, only TNFRI has a cytoplasmic domain that triggers apoptosis. Both types of receptors can be released into solution and neutralize TNF-alpha's biological activity. TNF alpha, a proinflammatory cytokine with multiple functions, is part of the tumor necrosis factors (TNF) superfamily.