TNF-alpha(Tumor Necrosis Factor alpha)
Synonym:
Structure/FunctionTNF-alpha is a member of a family of cytokines which also includes LIF , CNTF , Oncostatin M , ILI1 , and CT-1 . All known members of the TNF-alpha cytokine family induce hepatic expression of Acute phase proteins .
TNF-alpha is produced by many different cell types. The main sources in vivo are stimulated monocytes, fibroblasts, and endothelial cells. Macrophages, T-cells and B-lymphocytes,granulocytes, smooth muscle cells, eosinophils, chondrocytes, osteoblasts, mast cells, glial cells,and keratinocytes also produce TNF-alpha after stimulation. Glioblastoma cells constitutively produce TNF-alpha and the factor can be detected also in the cerebrospinal fluid. Human milk also contains TNF-alpha.
Physiological stimuli for the synthesis of TNF-alpha are IL-1 , bacterial endotoxins , TNF , PDGF , and Oncostatin M . In fibroblasts the synthesis of TNF-alpha is stimulated by IFN-beta , TNF-alpha , PDGF , and viral infections. In thymic stromal cells the synthesis of TNF-alpha can be induced by NGF . TNF-alpha can also stimulate or inhibits its own synthesis, depending upon the cell type.In epithelial,endothelial, and fibroblastic cells secretion of TNF-alpha is induced by IL-17 .
TNF-alpha is a protein of 185 amino acids glycosylated at positions 73 and 172. It is synthesized as a precursor protein of 212 amino acids. Monocytes express at least five different molecular forms of TNF-alpha with molecular masses of 21.5-28 kDa. They mainly differ by post-translational alterations such as glycosylation and phosphorylation.
The human TNF-alpha gene has a length of approximately 5 kb and contains five exons. It maps to human chromosome 7p21-p14 between the markers D7S135 and D7S370. The murine gene maps to chromosome 5. The nucleotide sequences of TNF-alpha and G-CSF genes resemble each other in a way suggesting a possible evolutionary relationship.
GenBank (through Genome Net)
Sequence Information
Journal Information
last updated 11/12/98