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• W1602514569 endingPage "726" @default.
• W1602514569 startingPage "669" @default.
• W1602514569 abstract "Tumor necrosis factor (TNF) is a typical member of the polypeptide mediator family consisting of soluble factors like the interferons, interleukins, and hematopoietic growth factors. Although the main producer cells of TNF are monocytes/macrophages and lymphocytes, many other cells of the body are capable of producing TNF. Consistent with its pleiotropic cellular interactions virtually all cells and tissues are potential targets of TNF action. The control of cellular TNF responsiveness is of extraordinary complexity. First, TNF production is tightly regulated and gives rise to two distinct forms of the bioactive molecule. The active soluble cytokine is proteolytically derived from a membrane-integrated precursor molecule which itself is able to signal in a juxtacrine situation. All typical cellular TNF responses are initiated by specific binding to two homologous receptors which are members of the growing TNF receptor superfamily. These receptors also bind lymphotoxin α and are coexpressed in most cells, although in different proportions. Upon ligand binding, they activate a complex pattern of intracellular signals in a cooperative mode. Both receptors are subject to multiple regulatory mechanisms. Upon stimulation, the extracellular domains can be cleaved proteolytically, giving rise to molecules with inhibitor/storage properties. Besides signaling via receptors, TNF has a lectin-like sugar binding activity, the biological role of which is far from being understood. Our present understanding of the biological role of TNF comes from both studies defining the conditions of TNF gene expression and investigations unraveling the multiple facets of TNF action. An enormous number of publications has enlightened cellular TNF effects in vitro demonstrating a striking diversity. This multitude of phenotypic and functional changes inducible by TNF must depend on a diversification of intracellular signaling mechanisms. However, the biological role of TNF in vivo is just beginning to be understood. Obviously, TNF-mediated effects show two sides. On the one hand, evidence is growing that TNF is involved in a number of pathophysiological processes, for example, rheumatoid arthritis, cerebral malaria, and AIDS. On the other hand, TNF is believed to be crucial in the successful development of antibacterial immune responses." @default.
• W1602514569 created "2016-06-24" @default.
• W1602514569 creator A5056350199 @default.
• W1602514569 creator A5060416268 @default.
• W1602514569 date "1997-01-01" @default.
• W1602514569 modified "2023-09-25" @default.
• W1602514569 title "Tumor necrosis factor" @default.
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