From CellBiology
Revision as of 10:39, 18 May 2009 by Z3186815 (talk | contribs)

Tumor Necrosis Factor Alpha


Tumor Necrosis Factor Alpha (TNF-α) belongs to the Tumor Necrosis Factor superfamily (Member 2). It is. It was first discovered by Carswell et al. in 1975 in mouse serum after injection with Mycobacterium bovis strain bacillus Calmette-Guerin (BCG) and endotoxin [1]. TNF-α is now often recognized under various other titles including simply Tumor Necrosis Factor (TNF); TNFA, Cachectin, Monocyte-derived TNF, Macrophage-derived TNF [1] and is now known to be one of the most significant members of its class. This serum glycoprotein is a potent cytokine responsible for initiating a broad spectrum of processes that can have effects at both the cellular and systemic levels. Activation of these processes occurs upon binding of the protein to its various cell-surface receptors. TNF-α is predominantly produced and secreted (in soluble form) by activated monocytes/macrophages during the inflammatory response (acute and chronic) however, TNF-α is also produced by other mononuclear leukocytes [2]. Since TNF-α is a potent inflammatory glycoprotein, its production is typically stimulated by both exogenous and endogenous factors including bacteria, viruses, and other cytokines [3]. Bacteria cell walls contain lipopolysaccharides which are a particularly potent stimulus for TNF-A synthesis [4]. With a diverse range of regulative effects on biologic processes, TNF-α is involved in lipid metabolism, coagulation, cell proliferation, differentiation, apoptosis, necrosis, insulin resistance, and endothelial function, amongst various other processes [5]. Previous studies also reveal that TNF-α has been implicated in the induction of a variety of pathologic conditions including autoimmune diseases, insulin resistance, and cancer [1] where much of these studies involved experimentation using knockout mice models to demonstrate and better understand the role of TNF-α in the human body.

Structure and Gene

TNF-α was initially identified in its soluble, cleaved form of approximately 17-kD, however with further research it was later identified in its insoluble, non-cleaved form of approximately 26-kD, existing as a trans-membrane protein (Perez, et al., 1990). TNF-α is currently described as a homotrimeric protein which is encoded within the Major Histocompatibility Complex (MHC)[3] and has been mapped to chromosome 6p21.3 [REFERENCE]. The following is a link to an interactive murine model of TNF-α.