Disease relevance of Tumor necrosis factor

• Disruption of the LT/TNF/LIGHT network alleviates inflammation in certain autoimmune disease models, but decreases resistance to selected pathogens [1].
• Tumor necrosis factor receptor: Fc fusion protein in septic shock [2].
• Tumor necrosis factor (TNF) is a monocyte-derived cytotoxin that has been implicated in tumor regression, septic shock, and cachexia [3].
• Tumor necrosis factor-alpha and disease progression in multiple sclerosis [4].
• CD30 antigen, a marker for Hodgkin's lymphoma, is a receptor whose ligand defines an emerging family of cytokines with homology to TNF [5].
• By specifically targeting soluble TNF-alpha, Qbeta-C-TNF(4-23) immunization has the potential to become an effective and safe therapy against inflammatory disorders, which might overcome the risk of opportunistic infections associated with the currently available TNF-alpha antagonists [6].
• Our results suggest that fibroblasts, B and T lymphocytes support OC formation by producing RANKL, TNFalpha, and IL-7, contributing to the aggressive bone resorption in PsA patients [7].
• Over a median followup time of 17 months, the rate of hospitalization with a confirmed bacterial infection was 2.7% among the patients treated with TNFalpha antagonists compared with 2.0% among the patients treated with MTX only [8].
• We suggest that the increase of TNF-alpha and IL-1beta, as seen in infectious and autoimmune diseases, impairs clock gene functions and causes fatigue [9].
• This circuit bears a resemblance to the switch in TNFalpha function that has been observed during the resolution of bacterial infections [10].

Psychiatry related information on Tumor necrosis factor

• Tumor necrosis factor (TNF) alpha initiates the cytokine cascade, and high levels are associated with dementia and atherosclerosis in persons aged 100 years [11].
• The development of resistance to host defense mechanisms such as tumor necrosis factor (TNF)- and Fas-mediated apoptosis of transformed or virus-infected cells may be a critical component in the development of disease [12].
• Following sleep deprivation, alcoholics showed greater nocturnal levels of IL-6 and greater nocturnal increases of TNF as compared to controls [13].
• Within the 24 h TNF declined significantly in the therapy group (p = 0.006), while IL-6 showed a significant increase (p = 0.043) [14].
• Tumor necrosis factor-alpha, microglia and astrocytes in AIDS dementia complex [15].
• Monocyte production of TNFalpha did not change following psychological stress in RA patients taking TNFalpha antagonists or in healthy controls [16].

High impact information on Tumor necrosis factor

• Tumor necrosis factor (TNF) is a proinflammatory cytokine that induces conflicting pro- and antiapoptotic signals whose relative strengths determine the extent of cell death [17].
• Here we report an experimental and computational analysis of crosstalk between prodeath TNF and prosurvival growth factors in human epithelial cells [17].
• The proinflammatory cytokine tumor necrosis factor (TNF) alpha signals both cell survival and death [18].
• Tumor-necrosis factor (TNF), a pleiotropic cytokine, triggers physiological and pathological responses in several organs [19].
• In a liver regeneration model that requires TNF signaling, Timp3(-/-) mice succumbed to liver failure [19].

Chemical compound and disease context of Tumor necrosis factor

• Suramin also shows similar effects in in vivo models: apoptotic liver damage induced by CD95 stimulation and endotoxic shock mediated by tumor-necrosis factor (TNF) are inhibited in mice, but necrotic liver damage is not inhibited in a rat model of liver transplantation [20].
• Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock [21].
• BACKGROUND & AIMS: Treatment with a chimeric anti-tumor necrosis factor (TNF) antibody (infliximab) has been shown to be highly efficient for patients with steroid-refractory Crohn's disease (CD) [22].
• Hyperthermia had minimal effect as a sole agent but enhanced the effects of carboplatin and TNF in DLD-1 and HCT-15 cells [23].
• Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Is Required for Tumor Necrosis Factor {alpha}-Mediated Sensitization of Human Breast Cancer Cells to Chemotherapy [24].

Biological context of Tumor necrosis factor

• Tumor necrosis factor: an apoptosis JuNKie [25]?
• This hepatocyte cell death was completely rescued by a neutralizing antibody to TNF [19].
• Tumor necrosis factor (TNF) mediates a variety of biological activities including cell proliferation, differentiation and programmed cell death [26].
• These data indicate that TIMP3 is a crucial innate negative regulator of TNF in both tissue homeostasis and tissue response to injury [19].
• Hepatocytes from Timp3(-/-) mice completed the cell cycle but then underwent cell death owing to sustained activation of TNF [19].

Anatomical context of Tumor necrosis factor

• In contrast, septic shock and cachexia may result from either acute or chronic systemic activation of monocytes, resulting in the widespread release of TNF secretory component into the circulation of the affected individual [3].
• The increase in TNF in Timp3(-/-) mice culminated in hepatic lymphocyte infiltration and necrosis, features that are also seen in chronic active hepatitis in humans [19].
• The latent membrane protein 1 (LMP1) of EBV-infected cells plays a central part in this process by mimicking members of the family of tumor necrosis factor (TNF) receptors, thereby transmitting growth signals from the cell membrane to the nucleus through cytoplasmic TNF-receptor-associated factors (TRAFs) [27].
• Tumor necrosis factor (TNF) is synthesized by macrophages exposed to endotoxin [28].
• We show here that TNF markedly stimulates production of GM-CSF messenger RNA and protein in normal human lung fibroblasts and vascular endothelial cells, and in cells of several malignant tissues [28].

Associations of Tumor necrosis factor with other chemical compounds

• These results implicate integrin alphaVbeta3 in the anti-vascular activity of TNF and IFN-gamma and demonstrate a new mechanism by which cytokines control cell adhesion [29].
• The activation of the transcription factor nuclear factor-kappa B (NF-kappaB) by tumor necrosis factor (TNF), ionizing radiation, or daunorubicin (a cancer chemotherapeutic compound), was found to protect from cell killing [30].
• Previously, we showed that tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), and IL-8, are produced by PMN after stimulation with agonists, such as lipopolysaccharide (LPS) [31].
• Tumor necrosis factor (TNF) signals cell death and simultaneously induces generation of ceramide [32].
• Surgical or chemical vagotomy rendered animals sensitive to TNF release and shock, despite treatment with CNI-1493, indicating that an intact cholinergic antiinflammatory pathway is required for antiinflammatory efficacy in vivo [33].
• Stimulation of human umbilical arterial endothelial cells (HUAECs) or isolated human mononuclear cells with 1 microM Ang-II caused increased TNFalpha mRNA expression and protein [34].
• A significant decrease in synovial tissue lubricin gene expression was associated with elevated TNFalpha and IL-1beta concentrations in SF lavage samples [35].

Gene context of Tumor necrosis factor

• These observations raise the possibility that a surface LT alpha-LT beta complex may have a specific role in immune regulation distinct from the functions ascribed to TNF [36].
• However, NF-kappa B activation by TRADD is not inhibited by crmA expression, demonstrating that the signaling pathways for TNF-induced cell death and NF-kappa B activation are distinct [37].
• We conclude that Peg3 is a regulator of the TNF response [26].
• Dysregulation of TNF occurred specifically in Timp3(-/-), and not Timp1(-/-) mice [19].
• Tumor necrosis factor-alpha occupies a central role in rheumatoid arthritis (RA) pathogenesis [38].
• Cells treated with an IAC, or those in which cIAP1 was deleted, became sensitive to apoptosis induced by exogenous TNFalpha, suggesting novel uses of these compounds in treating cancer [39].
• These compounds inhibited association of TNFalpha receptor (TNFalphaR) I with TNFalphaR-associated death domain protein (TRADD) and receptor interacting protein 1 (RIP1), the initial intracellular signaling event following TNFalpha stimulation [40].
• By this mechanism, zinc suppressed LPS-induced activation of IkappaB kinase beta (IKKbeta) and NF-kappaB, and subsequent TNF-alpha production [41].
• Triggering with anti-beta(2)GPI antibodies induced IRAK phosphorylation and consequent NF-kappaB activation, which led to the release of TNFalpha and TF [42].
• Positive correlations were observed between TNFalpha and TTP, TNFalpha and TIA-1, TIA-1 and HuR, and TNFalpha and HuR gene expression in both healthy control subjects and patients with RA [43].
• While TNFalpha had no effect on MCL-1 transcription, it induced expression of another antiapoptotic molecule, BFL-1 [44].
• The negatively regulated AR gene chromatin region showed TNFalpha-dependent enrichment of B-myb and the NF-kappaB proteins p65 and p50 [45].

Analytical, diagnostic and therapeutic context of Tumor necrosis factor

• As a potent mediator of inflammation, the cytopathic cytokine, tumor necrosis factor (TNF) has been considered to be a strong candidate in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE) [46].
• Identification of new therapeutic targets for the management of septic shock remains imperative as all investigational therapies, including anti-tumor necrosis factor (TNF) and anti-interleukin (IL)-1 agents, have uniformly failed to lower the mortality of critically ill patients with severe sepsis [47].
• Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis [48].
• However, NIK was selectively required for gene transcription induced through ligation of LTbeta receptor but not TNF receptors [49].
• TNF receptor-associated factor (TRAF) proteins are candidate signal transducers that associate with the cytoplasmic domains of members of the tumor necrosis factor (TNF) receptor superfamily [50].

References