Tumor necrosis factor-α (cachectin) and tumor necrosis factor-β (lymphotoxin) are two closely related proteins that share sequence homology of 34% in their amino acid sequence. Both mediators act on their target cells via the same receptors and, therefore, show similar, but not identical, biological effects. Under denaturing conditions TNF-α is a 17-kilodalton, nonglycosylated protein. The biologically active form of TNF-α is a trimer. Besides this soluble form of TNF-α, a 28-kilodalton membrane-bound form occurs on cell surfaces of TNF-producing cells, which may serve as a pool for soluble TNF-α and can be proteolytically cleaved from the cell surface.
Different cells are shown to produce TNF-α: For example, macrophages, CD4+ T cells and NK cells after stimulation with lipopolysaccharides. Additionally, smooth muscle cells, polymorphonuclear neutrophils, astrocytes and a variety of tumor cell lines can produce TNF-α. TNF-α acts via two distinct cell surface receptors, which are called TNF receptor I, and TNF receptor II. These receptors can be identified on virtually all cell types except erythrocytes. Besides the cell-bound forms of TNF receptors, soluble forms are known to be capable of TNF-α binding. They compete, therefore, with the cell-bound forms and can inhibit the effects of TNF-α.
Due to the occurrence of TNF-α receptors on nearly all cells, TNF-α demonstrates a wide variety of biological action. It has cytolytic and cytostatic effects on tumor cells and shows chemotactic activity on neutrophils. TNF-α is a growth factor for fibroblasts and stimulates the synthesis of collagenase and prostaglandin E2 bone resorption can be induced by TNF-α because it activates osteoclasts. TNF-α enhances the proliferation of T cells after stimulation with IL-2. In the absence of IL-2, TNF-α induces the proliferation and differentiation of β cells.
References:
Buck C, Gallati H, Pohlandt F, et al. Increased levels of tumor necrosis factor alpha (TNF-alpha) in tracheal aspirates of newborns with pneumonia. Infection. 1994; 22(4):238-241. PubMed 8002082
Herbelin A, Nguyen AT, Zingraff J, et al. Influence of uremia and hemodialysis on circulating interleukin-1 and tumor necrosis factor alpha. Kidney Int. 1990; 37(1):116-125. PubMed 2299797
Jacob CO. Tumor necrosis factor alpha in autoimmunity: Pretty girl or old witch? Immunol Today. 1992; 13(4):122-125 (review). PubMed 1580993
Marano MA, Fong Y, Moldawer LL, et al. Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality. Surg Gynecol Obstet. 1990; 170(1):32-38. PubMed 2294627
Maury CP, Teppo AM. Raised serum levels of cachectin/tumor necrosis factor alpha in renal allograft rejection. J Exp Med. 1987; 166(4):1132-1137. PubMed 3309124
Tumor Necrosis Factor Alpha, Serum
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