Disease relevance of Tnf

• There is evidence that the cytokine tumor necrosis factor alpha (TNF-alpha) contributes to the pathogenesis of neurological autoimmune diseases such as multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) [1].
• These results suggest that the activation of NF-kappaB by TNF-alpha may play an important role in the production of cytokines and cell adhesion molecules from osteoblasts, leading to the promotion of bone resorption and inflammation [2].
• Tumor necrosis factor-alpha (TNF-alpha) plays a key role in inflammatory diseases such as rheumatoid arthritis and in postmenopausal osteoporosis [2].
• We thus examined the effect of TNF-alpha on the activation of NF-kappaB in rat osteoblast-like osteosarcoma cells (ROS17/2.8) [2].
• It is well established that endotoxemia disrupts reproductive capability, and several proinflammatory cytokines, especially IL-1 beta, IL-6, and TNF-alpha in the brain, have been implicated in this endocrine aberration [3].

Psychiatry related information on Tnf

• Tactile hypersensitivity (allodynia) is one component of a constellation of "illness behaviors" triggered by TNF-alpha [4].
• The release of proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) and nitric oxide by microglia has been implicated in neurotoxicity in chronic neurodegenerative diseases such as Alzheimer's disease [5].
• The pro-inflammatory cytokine tumor-necrosis factor-alpha (TNF-alpha) is elevated in several neuropathological states that are associated with learning and memory deficits [6].
• Its depletion caused by alcohol consumption amplifies the power of TNF-alpha to generate reactive oxygen species, compromising mitochondrial and cellular functions that culminate in cell death [7].
• Ethanol (ETOH) suppresses intrapulmonary TNF alpha and NO release and impairs pulmonary host defense mechanisms [8].

High impact information on Tnf

• TNF-alpha was chosen as the transcriptionally inducible target gene to be quantified in alveolar macrophages of control rat lung, as well as low- and high-challenge lungs stimulated by endotoxin and IFN-gamma nebulization [9].
• Using this approach, we demonstrated dose-dependent manifold upregulation of the ratio of TNF-alpha mRNA copies per one copy of PBGD mRNA in alveolar macrophages of the challenged lungs [9].
• Therapies that neutralize the function of TNF-alpha suppress rheumatoid arthritis (RA) but not osteoarthritis (OA) [10].
• Similarly, this IL-1beta- and TNF-alpha-induced formation of active 11beta-hydroxy glucocorticosteroids from inert 11-keto glucocorticosteroids by the 11beta-OHSD1 was shown in the Kiki cell line that expresses the stably transfected bacterial beta-galactosidase gene under the control of a glucocorticosteroids response element [11].
• Also, Lewis astrocytes produce TNF-alpha in response to IFN-gamma/IL-1 beta [1].

Chemical compound and disease context of Tnf

• Divergences in the regulatory pathways controlling TNF-alpha, IL-10, and IL-6 production in Kupffer cells following LPS or LTA stimulation may create a basis for understanding how the balance between pro- and anti-inflammatory cytokines is regulated in the liver following infections by gram-positive or gram-negative bacteria [12].
• The results indicate that intravenous administration of curcumin before the onset of sepsis attenuated tissue injury, reduced mortality, and decreased the expression of TNF-alpha in septic animals [13].
• Macrophages play a role in the initiation of bone resorption at the interface through the phagocytosis of cobalt chromium particles and subsequent release of TNF-alpha and PGE2 [14].
• Since increased TNF-alpha generation plays a pathogenic role in alcoholic liver disease, the DLPC action on Kupffer cells may explain, in part, its beneficial effects on liver cell injury after ethanol consumption [15].
• In C6 astrocytoma cell line and primary astrocytes, 5-AzadC enhanced proinflammatory cytokine (IFN-gamma, TNF-alpha, IL-1)-triggered NO synthesis in a time- and dose-dependent manner [16].

Biological context of Tnf

• We examined TNF-alpha gene expression by astrocytes derived from BN rats (resistant to EAE) and Lewis rats (highly susceptible) [1].
• However, suppression of TGF-beta(1)-induced apoptosis by EGF and TNF-alpha occurs via different protein kinase signaling pathways [17].
• Ceramide is a second messenger generated by TNF-alpha treatment and is an activator of JNK [18].
• Because this cytokine produced sustained activation of stress and proinflammatory kinases, we have explored the hypothesis that insulin resistance by TNF-alpha could be mediated by these pathways [19].
• Furthermore, TNF-alpha produced serine phosphorylation of IR and IRS-1 (total and on Ser(307) residue), and these effects were completely precluded by pretreatment with either PD169316 or salicylate [19].

Anatomical context of Tnf

• Expression of Tnf mRNA was significantly increased both in peritoneal leukocytes and in intestinal segments associated with implants in experimental animals [20].
• Peritoneal macrophages and neonatal microglia from Lewis and BN rats are responsive to both LPS and IFN-gamma priming signals for subsequent TNF-alpha production, suggesting that differential TNF-alpha expression by the astrocyte is cell type specific [1].
• TNF-alpha exerts damaging effects on oligodendrocytes, the myelin-producing cell of the central nervous system (CNS), and myelin itself [1].
• Intraperitoneal administration of IFN-gamma, TNF-alpha, and LPS led to rapid induction of iNOS mRNA in lipocytes, confirming in vivo the culture findings [21].
• Nitric oxide synthase was induced in vascular smooth muscle cells that had been exposed to interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) [22].

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

• ICAM-1-coupled signaling pathways in astrocytes converge to cyclic AMP response element-binding protein phosphorylation and TNF-alpha secretion [25].
• Formation of the TTF-2/DNA complex was decreased by TNF-alpha and/or IFN-gamma [26].
• TNF-alpha also induced the specific interaction of proteins from GMC nuclei with an oligonucleotide bearing the NF-kappa B binding sites in the VCAM-1 promoter [27].
• Smad3/4 binding was increased (p < 0.05) above controls with TNF-alpha and PYY reduced it by 40% [28].
• Scatchard analysis confirmed that TNF-alpha (100 ng/ml for 24 h) caused a decrease in the number of binding sites without change in VDR affinity [29].

Enzymatic interactions of Tnf

• Immunoblotting demonstrated that p42/44 MAPK was phosphorylated and RhoA protein was increased in bronchial tissue by TNF-alpha [30].
• Muscle levels of IGF-I mRNA and phosphorylated Akt were markedly reduced in ND animals with no change following anti-TNF-alpha therapy [31].
• Perfusion of TNF-alpha led to an increase in the levels of phosphorylated p38 MAPK detectable in the granule cells of the dentate gyrus [6].

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

• Astrocytes secrete TNF-alpha in response to LPS alone, and can be primed by IFN-gamma to enhance LPS-induced TNF-alpha production [1].
• In this study, we demonstrate that TGF-beta inhibits TNF-alpha expression, and induces/enhances IL-6 expression by primary rat astrocytes [33].
• Thus, parallel ROS-dependent and ERK1/2-dependent pathways converge to regulate TNF-alpha-induced MCP-1 gene expression in VSMCs [34].
• We found that LPS-induced TNF alpha is suppressed by pretreatment with the p38 mitogen-activated protein kinase (p38MAPK) inhibitor SB203580 [35].
• Semi-quantitative RT-PCR indicated that TNF-alpha also upregulated MMP-9 mRNA levels [36].

Other interactions of Tnf

• Inhibition of p38 and NF-kappaB activation by SB203580 and pyrrolidine dithiocarbamate, respectively, blocked endotoxin-induced H(2)O(2), NO, TNF-alpha, and IL-6 synthesis [23].
• We show that pretreatment with (10 ng/mL) EGF or (25 ng/mL) TNF-alpha can suppress TGF-beta(1)-induced apoptosis by 73% and 50%, respectively, in isolated rat hepatocytes [17].
• In both groups, cytokine mRNA levels all returned to baseline levels at 24 hours, while IL-1 beta, TNF-alpha, and TGF-beta 1 mRNA levels again rose significantly at 7 days only in animals with permanent LAD occlusion [37].
• In vitro stimulation of rat alveolar macrophages with IgG immune complexes greatly increased expression of mRNA and protein for MIP-2, CINC, MIP-1alpha, MIP-1beta, TNF-alpha, and IL-1beta [38].
• Glass fibers induced phosphorylation of MAP kinases, p38, and ERK in primary rat alveolar macrophages, and this phosphorylation was associated with TNF-alpha gene expression [39].

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].

References