||Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is mainly secreted by macrophages.TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF"s primary role is in the regulation of immune cells. Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases-autoimmune diseases, insulin resistance, and cancer.
|Biochem/physiol Actions :
||Tumor necrosis factor-α, also known as cachectin, is expressed as a 26 kDa membrane bound protein and is then cleaved by TNF-α converting enzyme (TACE) to release the soluble 17 kDa monomer, which forms homotrimers in circulation. TNF-α plays roles in antitumor activity, immune modulation, inflammation, anorexia, cachexia, septic shock, viral replication and hematopoiesis. TNF-α is expressed by a great variety of cells, with numerous inductive and suppressive agents. Primarily, TNF-α is produced by macrophages in response to immunological challenges such as bacteria (lipopolysaccharides), viruses, parasites, mitogens and other cytokines. TNF-α is cytotoxic for many transformed cells (its namesake activity) but in normal diploid cells, it can stimulate proliferation (fibroblasts), differentiation (myeloid cells) or activation (neutrophils). TNF-α also shows antiviral effects against both DNA and RNA viruses and it induces production of several other cytokines. Although TNF-α is used in clinical trials as an antitumor agent, TNF-α and the related molecule TNF-β (LT-α) share close structural homology with 28% amino acid sequence identity and both activate the same TNF receptors, TNFR1 and TNFR2. Mouse and human TNF-α share 79% amino acid sequence identity. Unlike human TNF-α, the mouse form is glycosylated.