Disease relevance of Tnfrsf1a

• Experimental intestinal endometriosis is characterized by increased levels of soluble TNFRSF1B and downregulation of Tnfrsf1a and Tnfrsf1b gene expression [1].
• In conclusion, protein deficiency in endotoxic rats increases the expression of TNFR-I and TNFR-II in all organs studied and TNF-alpha in selected ones [2].
• The presence of TNFR1 receptors, and perhaps their long-term activation or plasticity, may also play a critical role in the chronic allodynia and hyperreflexia observed after SCI or peripheral nerve damage [3].
• 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 [4].
• This is the first demonstration of a selective up-regulation of TNF-RI in cancer cachexia and suggests that local production of TNF-alpha and IL-6 is a corner-stone in the induction/maintenance of this syndrome [5].

High impact information on Tnfrsf1a

• Flow cytometric analyses using avian antibodies to purified rat p60 and p90 demonstrated that both proteins are present on rat monocytes and macrophages [6].
• The signaling is attributable to ligation of alveolar TNFR1 followed by receptor-mediated [Ca(2+)](i) increases and cPLA(2) activation in alveolar epithelium [7].
• In addition, AII increased p85 serine phosphorylation, inhibited the total pool of p85 associated PI 3-kinase activity, and decreased levels of the p50/p55 regulatory subunit of PI 3-kinase [8].
• Cg-induced hypernociception was abolished by administration of indomethacin plus guanethidine, diminished in TNF-R1-/- mice, and partially inhibited in WT mice pretreated with AbKC, IL-1ra, indomethacin, or guanethidine [9].
• IL-1ra and indomethacin pretreatment strongly inhibited the hypernociception induced by IL-1beta, which was not altered by AbKC or guanethidine or by knocking out TNF-R1 [9].

Chemical compound and disease context of Tnfrsf1a

• Overexpression of TNF and target genes, underexpression of TNF-receptor genes, and increased shedding of TNFRSF1B in this animal model provide further evidence for involvement of the TNF system in the pathogenesis of endometriosis [1].
• Ethanol exposure for 48 h increased TNF-R1 levels in human hepatoma cells in a dose-dependent manner [10].
• The aim of this study was to examine the role of TNF receptor I (TNF-RI) in the pathogenesis of heat-killed Corynebacterium parvum- and live bacillus Calmette-Guerin (BCG)-induced granulomas [11].
• In the present studies, insulin was found to stimulate in a rat hepatoma cell line (called FAO cells) the tyrosine phosphorylation of the 60-kilodalton p21ras GTPase-activating protein (GAP)-associated protein called p60 [12].
• Activation of protein kinase C stimulates the tyrosine phosphorylation and guanosine triphosphatase-activating protein association of p60 in rat hepatoma cells [12].

Biological context of Tnfrsf1a

• 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].
• Previous studies had shown that increasing energy intake in anorexic TNF-alpha-treated rats increased morbidity due to stabilization of TNF activity by soluble and membrane TNF receptors (TNFR) [2].
• In addition, recruitment of TNFR-activating factor 2 was likely promoted by Bcl10-mediated sequestering of cellular inhibitor of apoptosis protein 2 [13].
• The apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase, can mediate cell death downstream of TNFR1 [13].
• Co-immunoprecipitation analysis revealed a commensurate assembly of a TNFR1 scaffold complex containing TNFR-associated death domain protein, receptor interacting protein and TNFR-activating factor 2 [13].

Anatomical context of Tnfrsf1a

• TNFR1- and TNFR2-positive cells included neurons, astrocytes, and oligodendrocytes [14].
• In contused spinal cord, TNFR1 protein expression and immunoreactivity (IR) were detected as early as 15 min postinjury, reached its peak at 8 h, and declined markedly after 1 and 3 days postinjury [14].
• We detected strong immunoreactivity for TNFR1 and Fas in the somatolactotrope cell line GH3 [15].
• We correlated pain behavior in response to mechanical stimulation with immunoreactivity for TNF receptor (TNFR) 1 and 2 at 6, 24, 76 and 120 h following L5 and L6 spinal nerve ligation (SNL) [16].
• In L5 (injured) dorsal root ganglia (DRG), TNFR1 and TNFR2 levels displayed a bimodal increase, peaking at 6 and 120 h after SNL [16].

Associations of Tnfrsf1a 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 [14].
• A single injection of recombinant TNF receptor P75 (etanercept) was given subcutaneously 24 hours before the administration of LPS [17].
• In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release [18].
• Protection against liver injury by PGE1 or anti-TNF-alpha is associated with a reduction of TNF-R1 expression in hepatocytes [19].
• Similar results were also obtained between pulmonary TNF-alpha mRNA expression and myeloperoxidase activities (P<0.01), whereas there was a highly negative correlation between levels of renal TNFR-I mRNA expression and serum creatinine [20].

Physical interactions of Tnfrsf1a

• Following the exposure of oligodendrocytes to IFN-gamma, TNF-R1 expression was transcriptionally induced by the binding of signal transducer and activator of transcription (STAT-1) homodimers to the IFN-gamma activated site (GAS) present in the gene promoter [21].

Co-localisations of Tnfrsf1a

• 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 [22].
• In thymocytes, AQP-1 is present and was shown to colocalize with the plasma membrane receptor tumor necrosis factor receptor-1 (TNF-R1) both before and after the AVD, which suggests that this protein is not proteolytically cleaved and remains on the cell membrane [23].

Regulatory relationships of Tnfrsf1a

• In this study we show that the retinal autoantigen, S-antigen, contains a functional TNF-alpha homologous domain which stimulates maturation and differentiation of cultured dendritic cells (DC) or tissue DC via the p55 TNF-alpha receptor [24].

Other interactions of Tnfrsf1a

• The temporal pattern of TNFR2 expression was similar to that of TNFR1 but its expression peaked at 4 h postinjury [14].
• Subsequently, protein phosphatase 5 translocated into the nuclei of degenerating CA3 neurons, while ASK1 colocalized with the adaptor proteins Daxx and TNFR-activating factor 2 at the outer membrane of injured CA3 neurons [13].
• In the present work, we have assessed the effects on glomerular injury of blocking and binding of IL-1 to its receptor by rh IL-1 receptor antagonist (IL-1ra) and by neutralizing IL-1 and TNF with rm soluble IL-1 receptor type1 (sIL-1Rt1) and rh sTNF receptor (sTNFr p55), respectively [25].
• Isolated ECL cells were found to express the TNF receptor p55 and IFN-gamma receptor, but not the TNF receptor p75 or CD95 [26].
• Modulation of antibody-mediated glomerular injury in vivo by IL-1ra, soluble IL-1 receptor, and soluble TNF receptor [25].

Analytical, diagnostic and therapeutic context of Tnfrsf1a

• The increased shedding of TNFR1 was confirmed by Western blotting [27].
• Protein and mRNA expression of TNF-alpha, TNFR-I, and TNFR-II in liver, spleen, and gastrocnemius were measured by Western blot and RT-PCR, respectively [2].
• These CSF samples were analyzed by ELISA for the presence of TNF-alpha and soluble TNFR1 and TNFR2 (sTNFR1 and sTNFR2, respectively) [27].
• Effect of low-protein diet and protein supplementation on the expressions of TNF-alpha, TNFR-I, and TNFR-II in organs and muscle of LPS-injected rats [2].
• Repetitive intraperitoneal injection of Enbrel, a TNF receptor blocker, significantly decreased hepatocyte 8-OHdG levels and the frequency of deleted mtDNA while greatly extending graft survival time [28].

References