Disease relevance of Tnfrsf1b

• Experimental intestinal endometriosis is characterized by increased levels of soluble TNFRSF1B and downregulation of Tnfrsf1a and Tnfrsf1b gene expression [1].
• These results indicate that the sustained expression of TNF-R2 in AM by BLM exposure may sensitize these cells to TNF-a-mediated toxicity [2].
• The pattern of soluble TNF receptor p55 type 1 and p75 type 2 in reference to TNF-alpha and IL-1beta concentration in animals with experimental diffuse peritonitis (EDP) was estimated [3].
• When RG cells were infected, no infectious progeny virus particles were detected in tissue culture media and only five intracellular viral polypeptides could be detected using immune precipitation techniques (p75, p60, VP44, VP41, and VP19) [4].
• These results highlight the potential for TNF to play a vital role in inflammatory hyperalgesia, both by a direct action on neurons via TNFR1 and by facilitating the accumulation of macrophages in the DRG via a TNFR2-mediated pathway [5].

High impact information on Tnfrsf1b

• Recent studies have demonstrated that neurotrophins may also induce cell death via the p75 receptor [6].
• These data suggest that the mechanism of apoptosis by NGF through the p75 receptor is different from TNF and Fas-mediated killing. gamma Radiation of oligodendrocytes also activated a similar subset of caspases as NGF, indicating that NGF-induced oligodendrocyte apoptosis uses a similar cell death execution mechanism as injury models [7].
• Treatment with NGF causes long-term cultures of oligodendrocytes to die via a yet undefined mechanism mediated by the p75 neurotrophin receptor [7].
• Here, using MRI, we demonstrate that a focal intrastriatal injection of TNF-alpha causes a significant, acute reduction (15-30%) in cerebral blood volume (CBV), which is dependent on TNF-alpha-type 2 receptor (TNFR2) activation, and can be ameliorated by pre-treatment with a non-specific endothelin (ET) receptor antagonist [8].
• TNF-alpha reduces cerebral blood volume and disrupts tissue homeostasis via an endothelin- and TNFR2-dependent pathway [8].

Biological context of Tnfrsf1b

• Gene expression of Tnfrsf1a and Tnfrsf1b was downregulated in colon and small intestine of experimental animals, possibly as a mechanism of protection against TNF cytotoxicity [1].
• In vitro studies showed that pretreatment of naive AM with a TNF-R2 antibody significantly inhibited BLM-induced caspase-3 activity and apoptosis [2].
• In contrast, TNFR2 expression occurred exclusively on non-neuronal cells of the macrophage-monocyte lineage, with cell numbers increasing in a TNF-dependent fashion during CFA-induced arthritis [5].
• These data confirm the capacity of TNFR2 to generate an apoptotic cell death signal independent of TNFR1 [9].
• TRAF2 downregulation, which has been proposed as the mechanism by which TNFR2 enhances TNFR1 signaling, was observed in PC60 cells, but the TNRF1 signal was not modulated [9].

Anatomical context of Tnfrsf1b

• TNFR1- and TNFR2-positive cells included neurons, astrocytes, and oligodendrocytes [10].
• Time-dependent apoptosis of alveolar macrophages from rats exposed to bleomycin: involvement of tnf receptor 2 [2].
• In L5 (injured) dorsal root ganglia (DRG), TNFR1 and TNFR2 levels displayed a bimodal increase, peaking at 6 and 120 h after SNL [11].
• The spinal cord tissue was analyzed by immunohistochemistry for the expression of TNF-alpha, TNFR1, and TNFR2, and by the TUNEL technique for the occurrence of neuronal death [12].
• However, protein levels of TNF-alpha, TNF-R1, and TNF-R2 were all significantly increased in CFA-treated TMJ tissues [13].

Associations of Tnfrsf1b with chemical compounds

• Methylprednisolone (MP), a synthetic glucocorticoid, partially inhibited the injury-induced expression of TNFR1 and TNFR2, an effect which could be reversed by RU486, an antagonist of glucocorticoid receptors [10].
• Neurotrophic factors regulate neuronal survival and differentiation and control neurite outgrowth by binding to tyrosine kinase receptors, the Trks, and a tumor necrosis factor (TNF) receptor-like molecule, p75 neurotrophin receptor [14].
• HSC apoptosis in tissue culture in the presence of serum was quantified after addition of 0.1 to 100 ng/ml of nerve growth factor (NGF) a ligand for p75, by in situ counting of apoptotic bodies after addition of acridine orange [15].
• In view of the pro-survival roles described for trks and the context-dependent stimulation of survival and cell death pathways activated by p75, differential regulation of these receptors by estrogen is likely to alter neurotrophin-dependent cell signaling [16].
• Destruction of p75-expressing fibers in the superficial dorsal horn by 192-IgG saporin was not accompanied by changes in acetylcholine or norepinephrine content or by reduction in cholinergic neuronal number in the spinal cord dorsal horn [17].

Other interactions of Tnfrsf1b

• The temporal pattern of TNFR2 expression was similar to that of TNFR1 but its expression peaked at 4 h postinjury [10].
• BLM exposure had no marked effect on AM expression of TNF-R1 or caspase-8 activation, but significantly increased the expression of TNF-R2 that was accompanied by a rise in c-IAP1 and a decrease in TRAF2 [2].
• Receptors mRNAs, except TNF receptor 2 and gp130 mRNAs, showed temporal profiles that were similar to those of their cytokine mRNAs [18].

Analytical, diagnostic and therapeutic context of Tnfrsf1b

• Using reverse transcription-polymerase chain reaction (RT-PCR) technique, the messenger RNA (mRNA) for tumor necrosis factor receptor type 2 (TNF-R2, 75/80 kDa) was detected in rat primary astrocytes, with much lower level of expression when compared to that for tumor necrosis factor receptor type 1 (TNF-R1, 55/60 kDa) [19].
• The 55kDa protein of TNFR-1 but not the 75kDa of TNFR-2 was detected by Western blot analysis [20].
• Using RT-PCR and Northern blotting TNFR1 and TNFR2 mRNAs were found to be constitutively expressed and increased after LPS [21].
• Surprisingly, we find that a purified preparation of OECs, selected on the basis of low-affinity nerve growth factor receptor (p75) expression, results in less extensive remyelination than an unpurified preparation following transplantation into areas of persistent demyelination in rodent CNS in the X-irradiation/ethidium bromide (X-EB) model [22].
• In situ hybridization was performed to assess the cellular localization of IGF-1, NGF, p75, and IGF-1R mRNA and immunohistochemistry served to localize the source of p75 and IGF-1R protein expression [23].

References