DefinitionThis section has been translated automatically.
Multifunctional proinflammatory cytokine centrally involved in local and systemic inflammation. TNF-alpha is one of the best studied members of the so-called TNF/TNFR superfamily, a cytokine system that plays central roles in the immune response and in organogenesis, especially of the lymphatic system. Thus, it plays a central role in the pathogenesis of psoriasis as well as other inflammatory processes (Crohn's disease, arthritides; pathogenesis of contact allergy). It causes hemorrhagic necrosis in certain tumors.
General informationThis section has been translated automatically.
TNF-α exists biologically in soluble or transmembrane-bound form. TNF-α molecules interact with at least 2 receptors (tumor necrosis factor receptor superfamily member 1A(TNFRSF1A) or tumor necrosis factor receptor superfamily member 1B (TNFRSF1B). The interaction of TNF-α with its receptors activates signaling cascades that can lead to apoptosis (via caspase-8; see caspases below) and cell activation (via NF-κB) (Note: NF-kappaB (nuclear factor-kappa B) is a fast-acting primary transcription factor present in all cell types. It is involved in cellular responses to stimuli such as cytokines and stress and plays a key role in regulating the immunological response to infection/ see also under transcription factors).
The balance of antagonistic effects of both signaling inductions depends on the cellular environment in which stimulation by TNF-α occurs. The NF-κB-mediated reaction is relevant for inflammation, in the course of which proinflammatory enzymes such as interleukins (especially IL-6 and IL-8) are released.
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OccurrenceThis section has been translated automatically.
TNF-α is mainly produced and released by macrophages, but also by a large number of other cells such as lymphocytes, mast cells, endothelial cells, cardiac muscle cells, fibroblasts as well as neuronal tissue. Large amounts of TNF-α are released in response to bacterial products (e.g. lipopolysaccharides) as well as interleukin-1β. Its formation is stimulated via Toll-like receptors and the MAP pathway as well as NF-kappaB. Furthermore, it has effects on lipid metabolism, blood coagulation, insulin resistance and various endothelial functions.
TherapyThis section has been translated automatically.
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LiteratureThis section has been translated automatically.
- Alexis A et al (2005) Off-label dermatologic uses of anti-TNF-a therapies. J Cutan Med Surg 9: 296-302
- Wakefield PE, James WD et al (1991) Tumor necrosis factor. J Am Acad Dermatol 24: 675-685
- Carter PH et al (2001) Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-α. PNAS 98: 11879-11884
- Hehlgans, T et al (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115: 1-20
- Seneschal J et al (2007) Psoriasiform drug eruptions under anti-TNF treatment of arthritis are not true psoriasis. Acta Derm Venereol 87: 77-80
- Tracey KJ (2002) The inflammatory reflex. Nature 420: 853-859