[Biology of tumor necrosis factor type alpha (TNF-alpha)].

Tumor necrosis factor type alpha (TNF-alpha) is one of 22 TNF superfamily ligands. Its synthesis is regulated by expression of gene localized on chromosome 6. During posttranslation modification the proteolytic cleavage of the 76-aminoacid domain from the membrane-bound protein occurs with final formation of mature, biologically active, secreted TNF-alpha form. The effect on the target cells depends on the activation of specific surface receptors: TNFR1--is present on most nuclear cells and has affinity to both membrane-bound and secreted forms; TNFR2--is localized mostly on fibroblasts, endothelial cells, lymphocytes, macrophages, neutrophils and thymocytes, and is activated almost selectively by membrane-bound form. Depends on additional factors the TNFR1 activation may initiate apoptosis, or activation of pathways which depend on nuclear factor kappaB (NFkappaB) and c-Jun N-terminal kinase (JNK). Role of TNFR2 is unclear. TNF-a has multidirectional biological activity that include immunomodulation, oncostatic, osteolytic, pirogenic, proinflammatory and other effects.