IndraLab
Statements
reach
"Activation of the TNFR1 receptor on neurons initiates the caspase cascade involved in apoptosis [XREF_BIBR] Badiola et al. (2009) using TNFR KO mice and an OGD model in cortical cultures showed that TNF induced apopotic cell death involves TNFR1 activation of caspase-8 and caspase-3 but not caspase-9 [XREF_BIBR]."
reach
"The percentage of expression and MFI of TNFR1 was dramatically increased when ECFCs were treated with low doses of TNFalpha (0.01 and 0.1 ng/ml) and then reached to basal level in intermediate doses of 1 and 10ng/ml and elevated again following high doses of 50 and 100ng/ml of TNFalpha treatment."
sparser
"The destination depends on the modification states switching between ubiquitination and phosphorylation. xref On the condition that TNFR1 is activated by TNF-α, ubiquitination of RIPK1 by cIAPs and LUBAC results in cell alive through NF-κB signal pathway, xref and deubiquitination of RIPK1 leads to apoptosis xref or necroptosis which is determined by its phosphorylation states. xref Once phosphorylated, RIPK1 then catalyzes the phosphorylation of RIPK3, which launches necroptosis and can be inhibited by necrostatin-1 (Nec-1), the specific inhibitor of RIPK1."
reach
"Generally, stimulation of TNFRSF1A by TNF can result in the activation of MAPK (mitogen activated protein kinase) and NFKB and NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways and the transcription of prosurvival genes and proinflammatory cytokines, or the activation of cell death pathways such as extrinsic apoptosis or necroptosis."
eidos
"Complex I : stimulation of TNFR1 by TNF promotes the formation of an intracellular signalling complex associated with the death domain of trimerized TNFR1 that recruits two death domaincontaining proteins : adaptor protein TRADD and receptor-interacting serine / threonine-protein kinase 1 ( RIPK1 ) ."
reach
"To determine whether there were any functional differences in the ability of TNF and LTalpha3 to induce TNFR1 dependent apoptosis or necroptosis, and if there were different requirements for cIAPs and Sharpin to transmit the TNFR1 signal, we compared the ability of cells to respond to TNF and LTalpha3."
reach
"Although several cell lines that are sensitive to the Smac mimetic BV6 die in a TNFalpha dependent manner, A172 glioblastoma cells undergo BV6 induced apoptosis largely independently of TNFalpha and TNFR1, as the TNFalpha blocking antibody Enbrel or TNFR1 knockdown provide little protection."
reach
"XREF_BIBR, XREF_BIBR In contrast to the critical role of IFNbeta for BV6 and TMZ induced apoptosis that we discovered in the current study, we previously reported that TNFalpha, another prototypic NF-kappaB target gene, is largely dispensable for BV6 and TMZ induced apoptosis, as addition of the TNFalpha blocking antibody Enbrel or TNFR1 knockdown failed to rescue apoptosis upon combination treatment."
reach
"We infected primary human monocytes and monocyte derived macrophages with the virulent Mycobacterium tuberculosis strain H37Rv and followed the rate of cell death in the absence or presence of a wide concentration range of four different TNF targeted biologicals : infliximab and adalimumab (both monoclonal antibodies to human TNF) and etanercept and polyethylene-glycols TNFR1 (fusion constructs of human TNFR2 and TNFR1, respectively)."
"Tumour necrosis factor (TNF) exerts two main effects: a beneficial one as an anti-infection, anti-tumour cytokine, and a detrimental one in the systemic inflammatory response syndrome (SIRS). Two receptors (TNF-R) mediate these effects. two distinct types of TNF-Rs have been identified and molecularly cloned: TNF-R55 (also referred to as TNFR1, p55 or CD120a) and TNF-R75 (also called TNFR2, p75 or CD120b)"
reach
"This may explain why we see reduced efficacy with TNF small molecules when TNFR1 signalling is driven by very high TNF concentrations, although it should be noted that these concentrations typically exceed those measured in patients with autoimmune disease such as rheumatoid arthritis 27."
reach
"They function similarly to endogenous SMAC by antagonizing the inhibition of caspases mediated by XIAP and by inducing the auto-ubiquitination of cIAP1 or cIAP2; subsequent NF-kappaB-induced expression of TNFalpha further activates pro apoptotic TNFR1 (TNFalpha receptor) signaling [XREF_BIBR - XREF_BIBR]."
reach
"Excessive activation of TNFR1 by TNF leads to the apoptosis of hepatocytes, and thus leads to organ damage; however, membrane bound TNFR1 can be cleaved through proteolytic shedding of its ectodomain, which is dependent on activation of TNF converting enzyme (TACE, also known as ADAM17)."
sparser
"However, when the NF-κB-dependent response is inhibited, such as upon genetic deletion of NF-κB, expression of a dominant-negative form of IκBα or in the presence of transcriptional (actinomycin D) or translational (cycloheximide) inhibitors, cells succumb to TNFR1 activation by TNF [ xref , xref ]."
sparser
"These data not only indicate an important role for TNFR2 in DC survival, but also demonstrate that TNFR1- and TNFR2-mediated rescue is independent of each other and that sTNF is not capable of efficiently activating TNFR2 in moDC, whereas membrane-bound TNF potently activates both TNFR1 and TNFR2 in these cells."
reach
"To evaluate our hypothesis, RAW 264.7 macrophages were transduced with shRNA against PHB1, PHB2, or scrambled control (Scr), and then stimulated with lipopolysaccharides (LPS) or tumor necrosis factor-alpha (TNF-α), which activate lipid raft-dependent receptor signaling (CD14/TLR4 and TNFR1, respectively)."
reach
"It is known that TNF triggers the formation of a TNF receptor 1 (TNFR1) signaling complex by recruiting several effectors such as TNFR1 associated death domain protein (TRADD), receptor interacting protein kinase 1 (RIP1) and TNFR associated factor 2 (TRAF2) to mediate the activation of the transcription factor nuclear factor-kappaB (NF-kappaB) and mitogen activaed protein (MAP) kinases XREF_BIBR, XREF_BIBR."
reach
"Necroptosis can be induced through ligation of tumor necrosis factor (TNF) members (through TNFR1, TNFR2, TRAILR1, and TRAILR2), Fas ligand, toll like receptors, lipopolysaccharides (LPS), and genotoxic stress [XREF_BIBR - XREF_BIBR] As described earlier, ligation of TNFalpha activates TNFR1 and in turn induces the recruitment of RIP1 kinase via adaptor protein TRADD [XREF_BIBR, XREF_BIBR], to the membrane."
reach
"The finding that the TNFalpha activation of TNF-R1 signaling of apoptosis or survival is determined, at least in part, by integrin signaling is consistent with the report by other investigators that the matricellular protein known as CCN1 and CYR61 can cooperate with integrins alphavbeta5 and alpha6beta1 and the heparin sulfate proteoglycan-syndecan-4 on fibroblasts to promote TNFalpha pro apoptotic signaling."
sparser
"Two different problems needed to be solved for this approach: a) although TNFR1 is ubiquitously expressed, TNFR2 expression is much more restricted in terms of cell type, b) TNFR2 is efficiently activated only by mTNF which also activates TNFR1; TNFR1 can be activated by soluble TNF as well."
sparser
"TNF-α activation of TNFR1 has a pro-inflammatory effect (induction of NF-κB), and induces cell apoptosis (recruitment of TRADD (tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein), Fas associated via death domain, and then activation of caspases 8 and 3). xref "
sparser
"In summary, this study shows that sustained (but not short-term) hyperammonemia induces TNF-a expression in Purkinje neurons; this may be due to the activation of TNFR1 by TNF-a produced in glia (and later also by TNF-a produced in Purkinje cells), which induces the nuclear translocation of NF-κB and the induction of TNF-a mRNA transcription."
eidos
"Activation of TNFR1 by TNFalpha induces the formation of a membrane-associated , intracellular complex termed complex I. Complex I orchestrates a complex pattern of modifications on key regulators of TNF signaling that collectively determines the cell fate by activating pro-survival or executing cell death programs ."
reach
"Several studies have suggested a link between increased TNF-alpha levels and cognitive alteration, and a recent study showed that local increase of TNF-alpha in the hippocampal dentate gyrus activated astrocyte TNF receptor type 1 (TNFR1), which in turn triggered an astrocyte-neuron signaling cascade that resulted in persistent functional modification of hippocampal excitatory synapses."
reach
"It has been reported that apoptotic death receptors such as CD95 [XREF_BIBR], tumor necrosis factor related apoptosis inducing ligand receptor 1, tumor necrosis factor related apoptosis inducing ligand receptor 2 [XREF_BIBR], and tumor necrosis factor receptor 1 [XREF_BIBR] are enriched in the Golgi complex prior to transport to the plasma membrane, thus suggesting that the Golgi complex may play an important role in apoptotic signalling."
reach
"In contrast to wild-type soluble TNF (sTNF), which activates TNFR1 and induces cell death in L929 cells, none of the TNFR2-selective fusion proteins induced cell death in L929 cells (
Figure 2C
), verifying that fusion of IL2 to EHD2-sc-mTNF did not impact TNFR2 selectivity of this novel molecule."
reach
"These data show that the pathological changes of the glomerular endothelium and glomerular ESL are likely mediated by TNF-alpha released during endotoxemia and acting through TNFR1, since the LPS induced pathological changes were abolished in Tnfr1 -/- mice and administration of TNF alone induced similar pathological changes."
sparser
"TNF-α binds and activates Tumor necrosis factor receptor 1 (TNFR1), leading to the assembly of complex I, which is composed of TNF receptor-associated factor 2 (Traf2), TNFR1-associated death domain protein (TRADD), RIPK1, cellular inhibitor of apoptosis protein-1 (cIAP1), the tumor-suppressor cylindromatosis (CYLD) and the linear ubiquitin chain assembly complex (LUBAC)."
eidos
"The induction of apoptosis or necroptosis or triggering prosurvival NF-kappaB pathway upon stimulation of TNFR1 by TNF-alpha depends on the ubiquitination of RIP1 kinase and on the activity of caspase 8. RIP1 seems to be an important member in regulation of all abovementioned pathways since it is present in each of the three key complexes that mediate downstream signaling of TNFR1 ."
reach
"Importantly, it has been shown that local increase of TNFalpha in the hippocampal dentate gyrus activates astrocytic TNFR1, which in turn triggers an astrocyte-neuron signaling cascade that results in the persistent functional decline of hippocampal excitatory synapses [XREF_BIBR]."
reach
"Additionally, by activating TNFR1 in airway smooth muscle, TNF-alpha triggers extracellular signal regulated kinase (ERK) and p38 mitogen activated protein kinases (MAPKs) signaling pathway and transcription factors to turn on a variety of genes (interleukins) that mediate inflammatory and immune responses [XREF_BIBR]."
reach
"TNF-a released by glial cells activates TNFR1 in Purkinje neurons, leading to the nuclear translocation of NF-κB and the induction of TNF-a expression.The induction of TNF-a by sustained hyperammonemia may contribute to the neurological alterations observed in hyperammonemia and hepatic encephalopathy by altering the function of Purkinje neurons and neurotransmission and by inducing neuronal death.The trafficking and surface membrane expression of AMPA and NMDA receptors is altered by high levels of TNF-a [49–54]."
reach
"However, TNF-R1 is expressed in all studied cell lines and it was shown previously that TNF-R2 can induce apoptosis by strongly enhancing the activation of TNF-R1 by TNF-alpha and also by inhibiting nuclear factor kappa B mediated protection, indicating that TNF-R2 overexpression may sensitizes cells to TNF-a-mediated apoptotic signal after gamma irradiation."
reach
"The molecular mechanisms used by TNFR2 to activate BMX and PI3K/Akt are, however, poorly investigated and their relevance in macrophages has not been addressed so far.In sum, TNFR1 and TNFR2 are differently activated by soluble and membrane TNF, induce production of their own ligand in some cells, engage receptor-specific but also common pathways and the various TNFR1/2-associated signaling pathways are, last but not least, interconnected by regulatory circuits."
reach
"In these cells, this weak and late signal seemed to be strong enough to induce endogenous expression and secretion of TNF, which in an autocrine manner activated TNFR1 and subsequently the apoptotic signaling-cascade leading to Kym-1 cell death (XREF_FIG), as shown previously XREF_BIBR, XREF_BIBR."
eidos
"Generally , stimulation of TNFRSF1A by TNF can result in the activation of MAPK ( mitogen-activated protein kinase ) and NFKB / NF-kappaB ( nuclear factor kappa-light-chain-enhancer of activated B cells ) signaling pathways and the transcription of prosurvival genes and proinflammatory cytokines , or the activation of cell death pathways such as extrinsic apoptosis or necroptosis ."
sparser
"Excessive activation of TNFR1 by TNF leads to the apoptosis of hepatocytes, and thus leads to organ damage ( xref ); however, membrane-bound TNFR1 can be cleaved through proteolytic shedding of its ectodomain, which is dependent on activation of TNF-converting enzyme (TACE, also known as ADAM17) ( xref )."
sparser
"We have shown that induction of motor incoordination by hyperammonemia is mainly mediated by induction of microglia and astrocytes activation in cerebellum, which is associated to increased TNFα, which activates its receptor TNFR1, leading to increased NF-κB in microglia and expression of glutaminase, which increases glutamate, leading to reversal of the GABA transporter GAT3 function in activated astrocytes and increased GABAergic neurotransmission, finally inducing motor incoordination [ xref , xref , xref ]."
sparser
"Activation of TNFR1 by TNFα leads to the rapid recruitment of RIPK1, TNF receptor-associated death domain (TRADD), TNF receptor-associated factor 2 (TRAF2) and E3 ubiquitin ligases, cellular inhibitor of apoptosis protein 1/2 (cIAP1/2), to form complex I, also called TNFR1-signaling-complex (TNF-RSC), associated with the intracellular domain of TNFR1."
reach
"Since interaction of C12 with the plasma membrane results in TNF independent activation of TNFR1 mediated apoptotic signaling, we examined the subcellular localization of TNFR1, TRADD (TNF receptor associated death domain), DR5, the apoptotic adaptor protein FADD, caspase-8, and the vault components in CBM simulated by C12 or TNF."
reach
"Two different problems needed to be solved for this approach : a) although TNFR1 is ubiquitously expressed, TNFR2 expression is much more restricted in terms of cell type, b) TNFR2 is efficiently activated only by mTNF which also activates TNFR1; TNFR1 can be activated by soluble TNF as well."
reach
"Both C33Y TNFR1- and WT TNFR1 transfected SK-Hep-1 cells were treated with TNF-alpha under three different conditions : time course of response to constant exposure to 10 ng/mL TNF-alpha; pulse-chase response to 2 min exposure to 10 ng/mL TNF-alpha; dose response of exposure to various concentrations of TNF-alpha for 30 min."
reach
"However, our study highlights the fact that TNFalpha and TNFR1 is not the only death receptor ligand and receptor system that can mediate Smac mimetic induced apoptosis, as the TNFalpha blocking antibody Enbrel or TNFR1 knockdown largely fail to rescue BV6 induced apoptosis in A172 glioblastoma cells."
reach
"In contrast to a local secretion of TNFalpha by activated monocytes and macrophages in the intestinal lamina propria, it is also conceivable that systemic TNFalpha is elevated during alcoholic liver disease and activates TNFRI on intestinal epithelial cells to induce tight junction disruption."
reach
"Adenoviruses encode RID proteins that promote the internalization of death receptors for Fas, tumor necrosis factor related apoptosis inducing ligand (TRAIL), and tumor necrosis factor receptor 1 (TNFR1), thereby allowing infected cells to withstand these apoptotic stimuli [XREF_BIBR - XREF_BIBR]."
reach
"If the conditions are not sufficient to induce apoptotic cell death, pro inflammatory mediator TNF alphainitially activates TNFR1 and in turn recruits RIP1 to form complex I. Subsequently, these proteins combine with other components, and can be located in the cytosol in with complex IIb, which includes RIP1, RIP3, caspase-8 and FADD, further leading to necroptosis XREF_BIBR."
reach
"Local increase of TNFα in the hippocampal dentate gyrus activates astrocyte TNF receptor type 1 (TNFR1), which in turn triggers an astrocyte-neuron signaling cascade that results in persistent functional modification of hippocampal excitatory synapses which can lead to cognitive disturbance [54]."
reach
"XREF_BIBR Lastly, the infection studies in double TNF tm/tm x TNFR1 or R2 -/- transgenic mice rescued protection in TNF tm/tm x TNFR2 -/- mice and comparable protection in TNF tm/tm x TNFR1 -/- mice as in TNF tm/tm mice suggest that membrane signalling though TNFR2 likely provides host protection."
reach
"This occurs through a multicomponent pathway consisting of recruited hepatic macrophages that produce TNF (Figure 3), which, by engaging its type 1 receptor (TNFR1) on hepatocytes, leads to the induction of the critical lipogenic enzymes ACLY, ACC1, and FASN, which convert fructose-derived acetyl-CoA to C16 and C18 fatty acids (Todoric et al., 2020)."
reach
"96 As icariin is known to block the secretion of TNF-α,98 we speculated that icariin inhibits the TNF signaling pathway and TNFRSF1A to prevent AD progression.The autophagy-lysosome system plays an important role in the pathogenesis of AD.99 Genetic deficiency of MAPK14 stimulated autophagy, leading to reduced amyloid pathology via enhanced autophagic–lysosomal degradation of BACE1.99 Thus, the suppression of MAPK14 activity is a potential therapeutic strategy to mitigate neurodegeneration in AD."
reach
"Pre-incubation of CAR-GFP HBEC with TNFR1 blocking antibodies, at a concentration that completely blocked TNFalpha induced TNFR1 activation (Supp Fig. 1I), resulted in reduced THP-1 integration into CAR-GFP HBEC monolayers (XREF_FIG) thus confirming a requirement for TNFR1 in this process."
reach
"In summary, this study shows that sustained (but not short-term) hyperammonemia induces TNF-a expression in Purkinje neurons; this may be due to the activation of TNFR1 by TNF-a produced in glia (and later also by TNF-a produced in Purkinje cells), which induces the nuclear translocation of NF-κB and the induction of TNF-a mRNA transcription."
reach
"TNFR1, which is activated by both soluble and transmembrane TNF (with a higher affinity for soluble TNF) , is implicated in promoting pro-inflammatory responses , whereas, TNFR2, which is only fully activated by membrane-bound TNF, has been reported to mediate both neuroprotection and remyelination ."
reach
"Another category of molecules involved in cell communication that have been demonstrated to be essential to the ACAID mechanism comprises the secreted molecules and their receptors, including CXCR2, DR5, TNF related apoptosis inducing ligands (TRAIL), IFNgamma, IFNgammaR, IL-4, IL-13, IL-6, IL-10, TGFbetaRII, TNFRI, TNFRII, uPA, uPAR, plasminogen, substance P, and neurokinin A."
reach
"Together, these data indicated that loss of TNFA-R signaling or targeting of TNF-α by neutralizing antibody is protective against CCHFV.Histopathologically, TNFA-R DBL KO mice had a lesser degree of lytic necrosis on both days 4 and 10, compared to WT mice on day 4 (Fig 5A and 5B)."
reach
"When TNF-R1 and/or -R2 are stimulated by TNF-alpha, the extracellular portions of transmembrane proteins are cleaved, soluble ectodomains are released from the cell surface by a sheddase known as TNF converting enzyme (TACE) XREF_BIBR, and sTNF is neutralized by the sTNF-Rs XREF_BIBR."
sparser
"Membrane-bound and soluble TNF strongly interact with two receptors, TNFR1 and TNFR2, but the two forms of TNF are differentially effective in receptor activation. xref Whereas membrane-bound TNF activates TNFR1 and TNFR2 efficiently, soluble TNF is sufficient for TNFR1 activation but largely inactive upon binding to TNFR2."
reach
"We found that TRADD is essential for induction of the four most studied consequences of TNF induced TNFR1 signaling in mouse embryonic fibroblasts (MEFs), namely the activation of NF-kappaB, the activation of MAP kinases, the induction of necrotic cell death, and the initiation of apoptosis."
reach
"Activation of TNFR1 by TNFalpha leads to the rapid recruitment of RIPK1, TNF receptor associated death domain (TRADD), TNF receptor associated factor 2 (TRAF2) and E3 ubiquitin ligases, cellular inhibitor of apoptosis protein 1/2 (cIAP1/2), to form complex I, also called TNFR1-signaling-complex (TNF-RSC), associated with the intracellular domain of TNFR1."
reach
"An additional line of evidence against a role for p55 mediated T cell apoptosis in the control of autoimmune T cells by TNF may be the fact that lack of p55 mediated T cell removal, reflected by enhanced responses to secondary challenge in p55 -/ - and p55p75 -/ - mice, is not observed in TNF -/ - mice, implying a TNF independent role for the p55 TNFR in this process."
reach
"Under conditions that are insufficient to trigger apoptosis, TNFalpha activates TNFR1 and in turn induces the recruitment of receptor interacting protein 1 (RIP1) kinase and other proteins to form complex I. Subsequently, these proteins dissociate from TNFR1 and RIP1 can be found in the cytosol in complex IIb, which includes RIP1, receptor interacting protein 3 (RIP3) kinase, caspase-8 and FADD."
reach
"TNF, via p75, elicits potent EC activating cytokine and growth factor signaling that induces EC/EPC survival, migration, recruitment and incorporation into new tumor microvasculature and angiogenesis; whereas activation of p55 signaling by TNF leads to inhibition of EC migration and increase in EC apoptosis."
reach
"Consistent with a previous study, 29 autocrine TNFalpha signaling is not involved in BV6 and Drozitumab mediated apoptosis, as pharmacological or genetic inhibition of TNFalpha and TNFR1 signaling by the TNFalpha blocking antibody Enbrel or by RNA interference mediated silencing of TNFR1 failed to prevent BV6 and Drozitumab induced apoptosis."
reach
"TNFR1 can be activated by both soluble and membranous forms of TNF-α, but TNFR2 requires activation by membrane-bound TNF-α.8 A prior study by Hamid et al9 showed that although both the receptors mediate oxidative stress and diastolic dysfunction post-MI, global TNFR1 mice exhibit improved LV remodeling and contractile function, and global TNFR2 mice show exaggerated tissue remodeling during chronic HF.9 Similarly, Duerrschmid et al10 showed that in response to angiotensin II, TNFR1 mice develop less cardiac hypertrophy, remodeling, and hypertension compared with wild-type (WT) and TNFR2 mice."
reach
"The results suggest that hyperammonemia induces TNF-a in glial cells and that TNF-a released by glial cells activates TNFR1 in Purkinje neurons, leading to NF-kappaB nuclear translocation and the induction of TNF-a expression, which may contribute to the neurological alterations observed in hyperammonemia and hepatic encephalopathy."
sparser
"Notably, TNFR1 is activated by both soluble and transmembrane TNF, whereas TNFR2 is primarily activated by transmembrane TNF. xref TNFR1 is expressed constitutively on most cell types and functions primarily in inflammatory and innate immune responses, while TNFR2 is inducible, mainly expressed by immune, neuronal, and endothelial cells, and functions to mediate homeostatic and regulatory effects. xref A brief comparison between TNFR1 and TNFR2 is outlined in xref ."
sparser
"Activation of TNFR1 by TNFα induces the formation of a membrane-associated, intracellular complex termed complex I. Complex I orchestrates a complex pattern of modifications on key regulators of TNF signaling that collectively determines the cell fate by activating pro-survival or executing cell death programs."
reach
"Tumor necrosis factor (TNF) activity was inhibited during the development of actively induced, chronic relapsing experimental allergic encephalomyelitis (CREAE) in Biozzi AB/H mice, using a mouse TNF specific (TN3.19.12) antibody and bivalent human p55 and p75 TNF receptor-immunoglobulin (TNFR-Ig) fusion proteins."
reach
"In AD, excessive TNF-alpha activated TNFR1 through high affinity binding [XREF_BIBR] and signaling accordingly suppresses Abeta degradation by reducing the expression of insulin degrading enzyme [XREF_BIBR] and affects Abeta production through upregulation of BACE expression [XREF_BIBR] and gamma-secretase activity [XREF_BIBR]."
eidos
"Upon inhibition or inactivation of caspase-8 and cellular Inhibitor of apoptosis protein 1/2 ( cIAP1 / 2 ) , activation of TNF receptor-1 ( TNFR1 ) by TNFalpha induces the formation of TNFR1 signaling complexes , leading to phosphorylation-dependent RIPK1 activation ( Weinlich et al , 2017 ) ."
reach
"These findings reveal the necessity of PLAD mediated, ligand independent TNFR1 dimerization for NF-kB activation, highlight the PLAD as central regulator of TNFalpha induced TNFR1 oligomerization, and demonstrate that TNFR1-mEos2 MEFs can be used to investigate TNFR1 antagonizing compounds employing single-molecule quantification and functional NF-kB assays at physiologic conditions."
eidos
"Fig. 1 : Complex I : stimulation of TNFR1 by TNF promotes the formation of an intracellular signalling complex associated with the death domain of trimerized TNFR1 that recruits two death domain-containing proteins : adaptor protein TRADD and receptor-interacting serine / threonine-protein kinase 1 ( RIPK1 ) ."
reach
"XREF_BIBR reported earlier that TNFR2 is a marker associated with increased suppression by human peripheral blood T reg cells, and recently, it was demonstrated that both an agonistic antibody for TNFR2 and a cross linked TNF multimer, which would also activate TNFR1, efficiently expanded T reg cells from healthy donors in vitro."
reach
"Tumor necrosis factor (TNF)-receptor-associated periodic fever syndrome (TRAPS) is a rare monogenic autoinflammatory disorder characterized by mutations in the TNFRSF1A gene, causing TNF-receptor 1 (TNFR1) misfolding, increased cellular stress, activation of the unfolded protein response (UPR), and hyperresponsiveness to lipopolysaccharide (LPS)."
reach
"The unexpected name giving apoptosis-inducing activity of the TWEAK/Fn14 system has been traced back to a cooperative indirect mechanism comprising (i) sensitization for death receptor-induced killing by depletion of protective TRAF2-cIAP1 and TRAF2-cIAP2 complexes, and (ii) cell-type-specific induction of TNF and subsequent stimulation of the prototypic death receptor TNFR1 ."
sparser
"In contrast to wild-type soluble TNF (sTNF), which activates TNFR1 and induces cell death in L929 cells, none of the TNFR2-selective fusion proteins induced cell death in L929 cells ( xref ), verifying that fusion of IL2 to EHD2-sc-mTNF R2 did not impact TNFR2 selectivity of this novel molecule."
reach
"For example, tumor necrosis factor-alpha (TNFα), a key proinflammatory cytokine, was shown to increase the frequency of excitatory postsynaptic currents (EPSCs) and N-methyl-D-aspartate (NMDA) currents in lamina II neurons by stimulating TNF receptor subtype-1 and 2 (TNFR1 and TNFR2) in an inflammatory pain model [15]."
reach
"In the Results, APG-1387 induces apoptotic cell death through engagement of TNFR1 by TNF-alpha signaling pathway section there was an error : ' We have investigated the expression of NF-kappaB1 and p50 and NF-kappaB2 and p52 by western blot after cells were incubated with various concentrations of APG-1387 '."
eidos
"Once triggered by TNF-alpha , Fas , TNF-alpha-related apoptosis-inducing ligands and TLR agonists , TNFR1 is activated to form a primary membrane complex known as complex I , which in turn leads to sequential formation of cytoplasmic complex II and the RIP1 / RIP3 / MLKL necrosome and activation of PGAM5 and Drp1 to cause mitochondrial fragmentation and release of intracellular contents such as HMGB1 outside of necrotic cells.9 ,40,41 Necroptosis occurs when caspase-8 activation fails or is inhibited after complex II formation.42 Several studies have reported that necroptosis is involved in the dysfunction of intestinal epithelial cells.43 ,44 Therefore , inhibition of necroptosis could ameliorate cell damage ."