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Gene Review

Tnf  -  tumor necrosis factor

Rattus norvegicus

Synonyms: Cachectin, RATTNF, TNF-a, TNF-alpha, Tnfa, ...
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Disease relevance of Tnf


Psychiatry related information on Tnf


High impact information on Tnf


Chemical compound and disease context of Tnf


Biological context of Tnf


Anatomical context of Tnf


Associations of Tnf with chemical compounds

  • Taken together, these results suggest that differential TNF-alpha gene expression in response to LPS and IFN-gamma is strain and cell specific, and reflects both transcriptional and post-transcriptional control mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)[1]
  • The differential TNF-alpha production by astrocytes from BN and Lewis strains is not due to the suppressive effect of prostaglandins, because the addition of indomethacin does not alter the differential pattern of TNF-alpha expression [1].
  • IGF-I inhibited, in a concentration-dependent manner, the production of nitrite and L-citrulline evoked by IL-1 beta or TNF-alpha [22].
  • Exogenous H(2)O(2) caused modest stimulation of TNF-alpha synthesis, did not affect the synthesis of NO or IL-6, and did not activate NF-kappaB or MAPKs [23].
  • Studies using an anti-type IIA sPLA2 antibody, sPLA2 inhibitors, and a type IIA sPLA2-specific antisense oligonucleotide revealed that IL-1 beta/TNF alpha-induced delayed PGE2 generation by these cells was largely dependent on inducible type IIA sPLA2, which was functionally linked to inducible COX-2 [24].

Physical interactions of Tnf


Enzymatic interactions of Tnf


Co-localisations of Tnf

  • TNF receptors TNFRI and TNFRII co-localized with biotinylated TNF-alpha tracer along the nerve trunk, suggesting that TNF-alpha transport may be receptor-mediated [32].

Regulatory relationships of Tnf


Other interactions of Tnf


Analytical, diagnostic and therapeutic context of Tnf

  • Kupffer cell activation plays a pivotal role in reperfusion injury, and Kupffer cell products, including free radicals and tumor necrosis factor alpha (TNF-alpha), are implicated as damaging agents [18].
  • However, TNF-alpha exposure of the cultures induced the expression of several inflammatory mediators, as determined by reverse transcription-PCR and ELISA [40].
  • ICAM-1 ligation by a mAb to rat ICAM-1 induced mRNA expression of proinflammatory cytokines such as IL-1alpha, IL-1beta, IL-6, and TNF-alpha [41].
  • Northern blot analysis revealed a marked increase in the mRNA levels of p105, a precursor of p50, 6 h after TNF-alpha and a gradual increase in p65 mRNA levels during the initial 1 h [2].
  • Electrophoretic mobility shift assay revealed that the activation of the p50-p65 heterodimer NF-kappaB was induced by TNF-alpha as early as 15 minutes followed by a persistent activation for 48 h [2].


  1. Differential tumor necrosis factor alpha expression by astrocytes from experimental allergic encephalomyelitis-susceptible and -resistant rat strains. Chung, I.Y., Norris, J.G., Benveniste, E.N. J. Exp. Med. (1991) [Pubmed]
  2. TNF-alpha increases expression of IL-6 and ICAM-1 genes through activation of NF-kappaB in osteoblast-like ROS17/2.8 cells. Kurokouchi, K., Kambe, F., Yasukawa, K., Izumi, R., Ishiguro, N., Iwata, H., Seo, H. J. Bone Miner. Res. (1998) [Pubmed]
  3. Hypothalamic interleukin-1 beta and tumor necrosis factor-alpha, but not interleukin-6, mediate the endotoxin-induced suppression of the reproductive axis in rats. Watanobe, H., Hayakawa, Y. Endocrinology (2003) [Pubmed]
  4. Immunocytochemical localization of TNF type 1 and type 2 receptors in the rat spinal cord. Holmes, G.M., Hebert, S.L., Rogers, R.C., Hermann, G.E. Brain Res. (2004) [Pubmed]
  5. Retinoic acid inhibits expression of TNF-alpha and iNOS in activated rat microglia. Dheen, S.T., Jun, Y., Yan, Z., Tay, S.S., Ling, E.A. Glia (2005) [Pubmed]
  6. Dissection of tumor-necrosis factor-alpha inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early-but not late-phase LTP. Butler, M.P., O'Connor, J.J., Moynagh, P.N. Neuroscience (2004) [Pubmed]
  7. Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor. Colell, A., García-Ruiz, C., Miranda, M., Ardite, E., Marí, M., Morales, A., Corrales, F., Kaplowitz, N., Fernández-Checa, J.C. Gastroenterology (1998) [Pubmed]
  8. Independent suppression of nitric oxide and TNF alpha in the lung of conscious rats by ethanol. Xie, J., Kolls, J., Bagby, G., Greenberg, S.S. FASEB J. (1995) [Pubmed]
  9. Real-time quantitative RT-PCR after laser-assisted cell picking. Fink, L., Seeger, W., Ermert, L., Hänze, J., Stahl, U., Grimminger, F., Kummer, W., Bohle, R.M. Nat. Med. (1998) [Pubmed]
  10. Beneficial autoimmunity to proinflammatory mediators restrains the consequences of self-destructive immunity. Wildbaum, G., Nahir, M.A., Karin, N. Immunity (2003) [Pubmed]
  11. Tumor necrosis factor alpha and interleukin 1beta enhance the cortisone/cortisol shuttle. Escher, G., Galli, I., Vishwanath, B.S., Frey, B.M., Frey, F.J. J. Exp. Med. (1997) [Pubmed]
  12. The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10. Dahle, M.K., Øverland, G., Myhre, A.E., Stuestøl, J.F., Hartung, T., Krohn, C.D., Mathiesen, Ø., Wang, J.E., Aasen, A.O. Infect. Immun. (2004) [Pubmed]
  13. The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-gamma. Siddiqui, A.M., Cui, X., Wu, R., Dong, W., Zhou, M., Hu, M., Simms, H.H., Wang, P. Crit. Care Med. (2006) [Pubmed]
  14. The effects of cobalt chromium upon macrophages. Horowitz, S.M., Luchetti, W.T., Gonzales, J.B., Ritchie, C.K. J. Biomed. Mater. Res. (1998) [Pubmed]
  15. Dilinoleoylphosphatidylcholine decreases acetaldehyde-induced TNF-alpha generation in Kupffer cells of ethanol-fed rats. Cao, Q., Mak, K.M., Lieber, C.S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  16. 5-Aza-2'-deoxycytidine stimulates inducible nitric oxide synthase induction in C6 astrocytoma cells. Cvetkovic, I., Popadic, D., Vuckovic, O., Harhaji, L.j., Miljkovic, D.j., Trajkovic, V. Brain Res. (2004) [Pubmed]
  17. The role of protein kinase B and mitogen-activated protein kinase in epidermal growth factor and tumor necrosis factor alpha-mediated rat hepatocyte survival and apoptosis. Roberts, R.A., James, N.H., Cosulich, S.C. Hepatology (2000) [Pubmed]
  18. Reperfusion after liver transplantation in rats differentially activates the mitogen-activated protein kinases. Bradham, C.A., Stachlewitz, R.F., Gao, W., Qian, T., Jayadev, S., Jenkins, G., Hannun, Y., Lemasters, J.J., Thurman, R.G., Brenner, D.A. Hepatology (1997) [Pubmed]
  19. Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner. de Alvaro, C., Teruel, T., Hernandez, R., Lorenzo, M. J. Biol. Chem. (2004) [Pubmed]
  20. Experimental intestinal endometriosis is characterized by increased levels of soluble TNFRSF1B and downregulation of Tnfrsf1a and Tnfrsf1b gene expression. Rojas-Cartagena, C., Appleyard, C.B., Santiago, O.I., Flores, I. Biol. Reprod. (2005) [Pubmed]
  21. Inducible nitric oxide synthase in rat hepatic lipocytes and the effect of nitric oxide on lipocyte contractility. Rockey, D.C., Chung, J.J. J. Clin. Invest. (1995) [Pubmed]
  22. Insulin-like growth factor I inhibits induction of nitric oxide synthase in vascular smooth muscle cells. Schini, V.B., Catovsky, S., Schray-Utz, B., Busse, R., Vanhoutte, P.M. Circ. Res. (1994) [Pubmed]
  23. Mechanisms of endotoxin-induced NO, IL-6, and TNF-alpha production in activated rat hepatic stellate cells: role of p38 MAPK. Thirunavukkarasu, C., Watkins, S.C., Gandhi, C.R. Hepatology (2006) [Pubmed]
  24. Cytosolic phospholipase A2 is required for cytokine-induced expression of type IIA secretory phospholipase A2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E2 generation in rat 3Y1 fibroblasts. Kuwata, H., Nakatani, Y., Murakami, M., Kudo, I. J. Biol. Chem. (1998) [Pubmed]
  25. ICAM-1-coupled signaling pathways in astrocytes converge to cyclic AMP response element-binding protein phosphorylation and TNF-alpha secretion. Etienne-Manneville, S., Chaverot, N., Strosberg, A.D., Couraud, P.O. J. Immunol. (1999) [Pubmed]
  26. Tumor necrosis factor-alpha and interferon-gamma suppress both gene expression and deoxyribonucleic acid-binding of TTF-2 in FRTL-5 cells. Miyazaki, A., Shimura, H., Endo, T., Haraguchi, K., Onaya, T. Endocrinology (1999) [Pubmed]
  27. Nuclear factor-kappa B mediates induction of vascular cell adhesion molecule-1 in glomerular mesangial cells. Khachigian, L.M., Collins, T., Fries, J.W. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  28. Peptide YY attenuates transcription factor activity in tumor necrosis factor-alpha-induced pancreatitis. Vona-Davis, L., Yu, A., Magabo, K., Evans, T., Jackson, B., Riggs, D., McFadden, D. J. Am. Coll. Surg. (2004) [Pubmed]
  29. Tumor necrosis factor alpha decreases 1,25-dihydroxyvitamin D3 receptors in osteoblastic ROS 17/2.8 cells. Mayur, N., Lewis, S., Catherwood, B.D., Nanes, M.S. J. Bone Miner. Res. (1993) [Pubmed]
  30. Involvement of p42/44 MAPK and RhoA protein in augmentation of ACh-induced bronchial smooth muscle contraction by TNF-alpha in rats. Sakai, H., Otogoto, S., Chiba, Y., Abe, K., Misawa, M. J. Appl. Physiol. (2004) [Pubmed]
  31. Tumor necrosis factor-alpha and malnutrition-induced inhibition of diaphragm fiber growth in young rats. Lewis, M.I., Da, X., Li, H., Fournier, M. J. Appl. Physiol. (2005) [Pubmed]
  32. Axonal transport of TNF-alpha in painful neuropathy: distribution of ligand tracer and TNF receptors. Shubayev, V.I., Myers, R.R. J. Neuroimmunol. (2001) [Pubmed]
  33. Differential modulation of astrocyte cytokine gene expression by TGF-beta. Benveniste, E.N., Kwon, J., Chung, W.J., Sampson, J., Pandya, K., Tang, L.P. J. Immunol. (1994) [Pubmed]
  34. Convergence of redox-sensitive and mitogen-activated protein kinase signaling pathways in tumor necrosis factor-alpha-mediated monocyte chemoattractant protein-1 induction in vascular smooth muscle cells. De Keulenaer, G.W., Ushio-Fukai, M., Yin, Q., Chung, A.B., Lyons, P.R., Ishizaka, N., Rengarajan, K., Taylor, W.R., Alexander, R.W., Griendling, K.K. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  35. Protein kinase C alpha requirement in the activation of p38 mitogen-activated protein kinase, which is linked to the induction of tumor necrosis factor alpha in lipopolysaccharide-stimulated microglia. Nakajima, K., Tohyama, Y., Kohsaka, S., Kurihara, T. Neurochem. Int. (2004) [Pubmed]
  36. Cytokine-mediated modulation of MMPs and TIMPs in multipotential neural precursor cells. Ben-Hur, T., Ben-Yosef, Y., Mizrachi-Kol, R., Ben-Menachem, O., Miller, A. J. Neuroimmunol. (2006) [Pubmed]
  37. Cytokine mRNA expression in postischemic/reperfused myocardium. Herskowitz, A., Choi, S., Ansari, A.A., Wesselingh, S. Am. J. Pathol. (1995) [Pubmed]
  38. Regulatory effects of eotaxin on acute lung inflammatory injury. Guo, R.F., Lentsch, A.B., Warner, R.L., Huber-Lang, M., Sarma, J.V., Hlaing, T., Shi, M.M., Lukacs, N.W., Ward, P.A. J. Immunol. (2001) [Pubmed]
  39. Activation of mitogen-activated protein kinase p38 and extracellular signal-regulated kinase is involved in glass fiber-induced tumor necrosis factor-alpha production in macrophages. Ye, J., Zeidler, P., Young, S.H., Martinez, A., Robinson, V.A., Jones, W., Baron, P., Shi, X., Castranova, V. J. Biol. Chem. (2001) [Pubmed]
  40. Tumor necrosis factor-alpha modulates the expression of its p60 receptor and several cytokines in rat tracheal epithelial cells. Bader, T., Nettesheim, P. J. Immunol. (1996) [Pubmed]
  41. ICAM-1-induced expression of proinflammatory cytokines in astrocytes: involvement of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways. Lee, S.J., Drabik, K., Van Wagoner, N.J., Lee, S., Choi, C., Dong, Y., Benveniste, E.N. J. Immunol. (2000) [Pubmed]
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