Disease relevance of Tnfrsf1b

• To analyze their function in toxoplasmosis, we orally infected mice genetically deficient for TNFR1 (TNFR1(0/0)), TNFR2 (TNFR2(0/0)), or both TNF receptors (TNFR1/2(0/0)), as well as wild-type (wt) mice with a low-virulent strain of Toxoplasma gondii [1].
• Precisely how TNF mediates protection against HSV-1 mortality in p55-/- p75-/- mice remains to be determined [2].
• Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG(35-55)-induced experimental autoimmune encephalomyelitis [3].
• Tumor necrosis factor-alpha impairs contact hypersensitivity induction after ultraviolet B radiation via TNF-receptor 2 (p75) [4].
• These results have important implications for therapies targeting p55 and p75 receptors for treating autoimmune diseases [3].

High impact information on Tnfrsf1b

• MemTNF-induced apoptosis was mediated through both TNF-R1 and TNF-R2 [5].
• The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI [6].
• Wild-type and TNFR2-deficient OT-I cells were activated and then deleted when transferred into RIP-mOVA mice, whereas CD95-deficient OT-I cells were not susceptible to deletion by cross-presentation [7].
• In the TNFR2-mediated signaling pathways, TRAF2 works as a mediator for activation signals such as NF-kappaB, but the role of TRAF1 has not been previously determined [8].
• Antiviral activity of tumor necrosis factor (TNF) is mediated via p55 and p75 TNF receptors [9].

Chemical compound and disease context of Tnfrsf1b

• Neurodegenerative and neuroprotective effects of tumor Necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2 [10].
• The contribution of both systems to renal fibrosis was assessed by treating TNFR1/TNFR2-double knockout (KO) mice with an angiotensin-converting enzyme inhibitor, enalapril [11].
• Synergism of Pseudomonas aeruginosa exotoxin A with endotoxin, superantigen, or TNF results in TNFR1- and TNFR2-dependent liver toxicity in mice [12].
• Transgenic Mice Expressing the p75 CCAAT-Displacement Protein/Cut Homeobox Isoform Develop a Myeloproliferative Disease-Like Myeloid Leukemia [13].

Biological context of Tnfrsf1b

• TNFR1-/- and TNFR2-/- mice displayed a normal spleen microarchitecture and mounted an IgM and IgG antibody response to SRBC [14].
• The induction of DNA synthesis and the suppression of apoptosis in response to nafenopin was abrogated completely by blocking antibodies to TNFR1 but not to TNFR2 [15].
• A similar response was seen in mice genetically deficient for either TNFR1, TNFR2, or both TNFRs, whereas IFN-gammaR-deficient (IFN-gammaR0/0) mice were found to be defective in the up-regulation of these molecules [16].
• We also determined whether activated p55(-/-) and p75(-/-) T cells differ in their sensitivity to cell death induced by TCR cross-linking [17].
• Glutamate-induced triggering of the ionotropic N-methyl-D-aspartate receptor was required for the enhanced and persistent phosphatidylinositol 3-kinase-dependent NF-kappa B activation by TNFR2, indicating a positive cooperation of TNF and neurotransmitter-induced signal pathways [18].

Anatomical context of Tnfrsf1b

• To determine whether TNF contributed to the bile duct damage seen in chronically-infected animals, we bred B6 mice with disrupted genes for Tnfrsf1a, Tnfrsf1b and Tnfsf5 [19].
• Therefore, the massive difference in magnitude for the secondary, although not the primary, response to these D(b)NP(366) and D(b)PA(224) epitopes cannot be considered to reflect differential TNFR2-mediated T cell editing [20].
• Collectively, our results provide evidence of a role for the p75 TNFR in cell death in that TNF signaling through TNFR2 sensitizes lymphoid cells for Fas-mediated apoptosis [21].
• Macrophages of tmTNFnc mice also produced less TNFR2 than WT macrophages (-30%) [22].
• In conclusion, an increase in tmTNF levels, rather than the lack of sTNF, significantly down-modulated TNFR2 synthesis in aortic endothelial cells, but had no major influence on the synthesis of some major pro-inflammatory and pro-atherothrombotic proteins [22].

Associations of Tnfrsf1b with chemical compounds

• Likewise, ethanol caused severe liver injury in wild-type mice (pathology score, 5.5 +/- 0.6) and TNF-R2 knockout mice (pathology score, 5.0 +/- 0.4), but not in TNF-R1 knockout mice (pathology score, 0.8 +/- 0.4; P < 0.001) [23].
• Tumor necrosis factor (TNF) alpha increases collagen accumulation and proliferation in intestinal myofibroblasts via TNF receptor 2 [24].
• To elucidate the neuroprotective signaling pathways of TNFR2, we investigated glutamate-induced excitotoxicity in primary cortical neurons [18].
• In vivo, intracameral injection of normal or TNFR1(-/-) 2,4,6-trinitrophenyl-coupled T cells into normal mice induced immune deviation, but TNFR2(-/-) 2,4,6-trinitrophenyl-coupled T cells were ineffective [21].
• Both phenol and croton oil painting onto the ears induced less inflammation in TNFR1(-) mice than normal and TNFR2(-) mice [25].

Physical interactions of Tnfrsf1b

• In contrast, p75 is nonredundantly coupled to sustained AKT activity and NF-kappaB activation in response to TCR/CD28-mediated stimulation [26].
• Expression of the p75 interleukin 2-binding protein on CD3+4-8-Tac- cells from autoimmune MRL/MP-lpr/lpr mice [27].

Regulatory relationships of Tnfrsf1b

• Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-methyl-D-aspartate receptor activation. Essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-kappa B pathway [18].
• TNFR2-induced persistent NF-kappa B activity was essential for neuronal survival [18].
• However, in contrast to WldS mice, in IL-6(-/-) mice we observed the characteristic lesion-induced invasion of macrophages and the upregulation of low-affinity neurotrophin receptor p75 (p75LNTR) mRNA levels identical to those of IL-6(+/+) mice [28].
• Combined stimulation with IFN-gamma/LPS enhances IL-12 p40 secretion and induces IL-12 p75 secretion by microglia [29].
• Comparison of platelets from +/+, TNFR1 -/- and TNFR2 -/- mice showed that caspases are activated mainly by the TNFR1 [30].

Other interactions of Tnfrsf1b

• These data thus demonstrate the utility of the two families of murine TNF receptor-specific mAbs and identify a novel function of the p75 TNF receptor in vivo [31].
• Spleen morphology and antibody response were investigated in wild-type, TNFR1-/-, TNFR2-/- and TNF/LT alpha-/- mice immunized with SRBC [14].
• Our observation that soluble p75 TNFR was elevated in the plasma of TNF-alpha-treated mice in comparison to untreated mice supports this hypothesis [32].
• This resistance to TCR-induced death in activated p75(-/-) CD8 T cells correlated with the resistance of these cells to Fas/Fas ligand-induced cell death [17].
• These observations suggest that the p75 TNFR may play a role in attenuating TNF-alpha-induced PAI-1 mRNA expression in acute inflammatory conditions [32].

Analytical, diagnostic and therapeutic context of Tnfrsf1b

• PMN numbers in bronchoalveolar lavage fluid recovered 21 h after cessation of exposure to O(3) (2 ppm, 3 h) were significantly increased compared with after air exposure but were not different in wild-type and p55/p75 TNFR -/- mice [33].
• METHODS: in situ hybridization with antisense 35S-labeled riboprobes for mRNA encoding both the p55 and p75 TNF receptor (TNFR) subtypes was used in normal and HSV-infected murine trigeminal ganglia [34].
• In retinal ischemia, we show early, transient upregulation of TNF, TNF receptor 1 (TNF-R1), and TNF-R2 6 hr after reperfusion preceding neuronal cell loss [10].
• The expressions of TNF receptor (TNFR)1 and TNFR2 mRNA in the liver were determined by Northern blot analysis [35].
• Evidence for TNFR1 expression on beta cells came from flow cytometry using monoclonal antibodies specific for TNFR1 and TNFR2 and from RT-PCR of beta cell RNA [36].

References