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TNFR2

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https://www.readbyqxmd.com/read/27899821/activation-of-tnfr2-sensitizes-macrophages-for-tnfr1-mediated-necroptosis
#1
Daniela Siegmund, Juliane Kums, Martin Ehrenschwender, Harald Wajant
Macrophages express TNFR1 as well as TNFR2 and are also major producers of tumor necrosis factor (TNF), especially upon contact with pathogen-associated molecular patterns. Consequently, TNF not only acts as a macrophage-derived effector molecule but also regulates the activity and viability of macrophages. Here, we investigated the individual contribution of TNFR1 and TNFR2 to TNF-induced cell death in macrophages. Exclusive stimulation of TNFR1 showed no cytotoxic effect whereas selective stimulation of TNFR2 displayed mild cytotoxicity...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27881867/endothelial-cell-colony-forming-units-derived-from-malignant-breast-diseases-are-resistant-to-tumor-necrosis-factor-%C3%AE-induced-apoptosis
#2
Chen-Pin Chou, Shih Sheng Jiang, Huay-Ben Pan, Yi-Chen Yen, Hui-Hwa Tseng, Yu-Ting Hung, Ssu-Han Wang, Yu-Lin Chen, Ya-Wen Chen
Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be elevated in certain malignant states. Using flow cytometry and a Hill-based colony forming unit (CFU) assay, the present study indicated that higher levels of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of endothelial cell colony-forming units (EC-CFUs) are associated with benign and malignant breast diseases, providing possible indicators for breast disease detection...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27864283/tumor-necrosis-factor-%C3%AE-a-key-contributor-to-intervertebral-disc-degeneration
#3
REVIEW
Cheng Wang, Xiaohua Yu, Yiguo Yan, Wei Yang, Shujun Zhang, Yongxiao Xiang, Jian Zhang, Wenjun Wang
Intervertebral disc (IVD) degeneration (IDD) is the most common cause leading to low back pain (LBP), which is a highly prevalent, costly, and crippling condition worldwide. Current treatments for IDD are limited to treat the symptoms and do not target the pathophysiology. Tumor necrosis factor-α (TNF-α) is one of the most potent pro-inflammatory cytokines and signals through its receptors TNFR1 and TNFR2. TNF-α is highly expressed in degenerative IVD tissues, and it is deeply involved in multiple pathological processes of disc degeneration, including matrix destruction, inflammatory responses, apoptosis, autophagy, and cell proliferation...
November 17, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27858345/myocardial-123-i-mibg-scintigraphy-in-relation-to-markers-of-inflammation-and-long-term-clinical-outcome-in-patients-with-stable-chronic-heart-failure
#4
Derk O Verschure, René Lutter, Berthe L F van Eck-Smit, G Aernout Somsen, Hein J Verberne
AIM: Chronic heart failure (CHF) results in both increased cardiac sympathetic activity and myocardial inflammation. The aim of this study was to identify the relationship between severity of heart failure (i.e., NT-proBNP and LVEF), cardiac sympathetic activity ((123)I-mIBG scintigraphy), and measures of inflammation in subjects with stable, optimally treated CHF. In addition, the predictive value for cardiac events (i.e., ventricular arrhythmia, progression of CHF and cardiac death) of (123)I-mIBG parameters and these inflammatory markers was evaluated...
November 17, 2016: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/27832801/gene-expression-comparison-reveals-distinct-basal-expression-of-hox-members-and-differential-tnf-induced-response-between-brain-and-spinal-cord-derived-microvascular-endothelial-cells
#5
Yves Molino, Françoise Jabès, Amandine Bonnet, Nicolas Gaudin, Anne Bernard, Philippe Benech, Michel Khrestchatisky
BACKGROUND: The heterogeneity of endothelial cell types underlies their remarkable ability to sub-specialize and provide specific requirements for a given vascular bed. Here, we compared rat microvascular endothelial cells (MECs) derived from the brain and spinal cord in both basal and inflammatory conditions. METHODS: We used whole rat genome microarrays to compare, at different time points, basal and TNF-α-induced gene expression of rat MECs from in vitro models of the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB)...
November 10, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27791020/essential-protective-role-of-tumor-necrosis-factor-receptor-2-in-neurodegeneration
#6
Yun Dong, Roman Fischer, Petrus J W Naudé, Olaf Maier, Csaba Nyakas, Maëlle Duffey, Eddy A Van der Zee, Doortje Dekens, Wanda Douwenga, Andreas Herrmann, Eric Guenzi, Roland E Kontermann, Klaus Pfizenmaier, Ulrich L M Eisel
Despite the recognized role of tumor necrosis factor (TNF) in inflammation and neuronal degeneration, anti-TNF therapeutics failed to treat neurodegenerative diseases. Animal disease models had revealed the antithetic effects of the two TNF receptors (TNFR) in the central nervous system, whereby TNFR1 has been associated with inflammatory degeneration and TNFR2 with neuroprotection. We here show the therapeutic potential of selective inhibition of TNFR1 and activation of TNFR2 by ATROSAB, a TNFR1-selective antagonistic antibody, and EHD2-scTNFR2, an agonistic TNFR2-selective TNF, respectively, in a mouse model of NMDA-induced acute neurodegeneration...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27777599/frailty-has-a-stronger-association-with-inflammation-than-age-in-older-veterans
#7
P Van Epps, D Oswald, P A Higgins, T R Hornick, H Aung, R E Banks, B M Wilson, C Burant, S Graventstein, D H Canaday
BACKGROUND: Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans. RESULTS: We analyzed 117 subjects (age range 62-95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty...
2016: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/27755992/a-new-form-of-amphotericin-b-the-complex-with-copper-ii-ions-downregulates-stnfr1-shedding-and-changes-the-activity-of-genes-involved-in-tnf-induced-pathways-amb-cu-2-downregulates-stnfr1-shedding-and-changes-the-activity-of-genes-involved-in-tnf-induced-pathways
#8
Joanna Gola, Barbara Strzałka-Mrozik, Celina Kruszniewska-Rajs, Adrian Janiszewski, Bartłomiej Skowronek, Mariusz Gagoś, Grzegorz Czernel, Urszula Mazurek
BACKGROUND: A new form of amphotericin B (AmB)- complex with copper (II) ions (AmB-Cu(2+)) - is less toxic to human renal cells. Cytokines, including Tumor Necrosis Factor (TNF), are responsible for nephrotoxicity observed in patients treated with AmB. Another problem during therapy is the occurrence of oxidized forms of AmB (AmB-ox) in patients' circulation. To elucidate the molecular mechanism responsible for the reduction of the toxicity of AmB-Cu(2+), we evaluated the expression of genes encoding TNF and its receptors alongside encoding proteins involved in TNF-induced signalization...
September 5, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27755542/selective-blocking-of-tnf-receptor-1-attenuates-peritoneal-dialysis-fluid-induced-inflammation-of-the-peritoneum-in-mice
#9
Florian Kälble, Janine Damaske, Danijela Heide, Iris Arnold, Fabian Richter, Olaf Maier, Ulrich Eisel, Peter Scheurich, Klaus Pfizenmaier, Martin Zeier, Vedat Schwenger, Julia Ranzinger
Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of peritoneal tissue integrity. The resulting structural and functional reorganization of the peritoneal membrane diminishes ultrafiltration rate and thereby enhances mortality by limiting dialysis effectiveness over time. Tumour necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are key players during inflammatory processes. To date, the role of TNFR1 in peritoneal tissue damage during PD-treatment is completely undefined...
2016: PloS One
https://www.readbyqxmd.com/read/27747245/tnf-%C3%AE-autocrine-feedback-loops-in-human-monocytes-the-pro-and-anti-inflammatory-roles-of-the-tnf-%C3%AE-receptors-support-the-concept-of-selective-tnfr1-blockade-in-vivo
#10
Jennie M Gane, Robert A Stockley, Elizabeth Sapey
Selective TNFR1 blockade in inflammatory diseases is emerging as a clinical strategy. We studied the roles of the two TNF-α receptors, TNFR1 and TNFR2, in human monocytes, the principal producer of TNF-α and central to many TNF-α driven diseases. We hypothesised that TNF-α has pro- and anti-inflammatory effects on monocytes, occurring differentially via TNFR1 and TNFR2. Monocytes were isolated from healthy human subjects and exposed to LPS, plus/minus the addition of blocking antibodies to TNF-α or its receptors...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27734832/corrigendum-tnfr2-expression-by-cd4-effector-t-cells-is-required-to-induce-full-fledged-experimental-colitis
#11
Xin Chen, Yingjie Nie, Haitao Xiao, Zhaoxiang Bian, Anthony J Scarzello, Na-Young Song, Anna L Trivett, De Yang, Joost J Oppenheim
No abstract text is available yet for this article.
October 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27671548/role-of-the-type-i-tumor-necrosis-factor-receptor-in-inflammation-associated-olfactory-dysfunction
#12
Davi Sousa Garcia, Mengfei Chen, Amy K Smith, Paulo Roberto Lazarini, Andrew P Lane
BACKGROUND: To understand mechanisms of human olfactory dysfunction in chronic rhinosinusitis, an inducible olfactory inflammation (IOI) model has been utilized to chronically express inflammatory cytokines locally, resulting in neuronal loss, diminished odorant responses, and repressed olfactory regeneration. Knockout of the minor tumor necrosis factor α receptor 2 (TNFR2) was previously shown to partially rescue these olfactory changes. The purpose of current study was to investigate the role of the major TNF receptor, TNFR1, in chronic olfactory inflammation...
September 27, 2016: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/27639923/tnf%C3%AE-in-the-regulation-of-treg-and-th17-cells-in-rheumatoid-arthritis-and-other-autoimmune-inflammatory-diseases
#13
Jonas Bystrom, F I Clanchy, Taher E Taher, Pam Mangat, Ali S Jawad, Richard O Williams, Rizgar A Mageed
TNFα is a principal pro-inflammatory cytokine vital for immunity to infections. However, its excessive production is involved in chronic inflammation and disease pathology in autoimmune diseases. Evidence for its pathogenic role is validated by the fact that its neutralisation by therapeutic agents in vivo is beneficial in ameliorating disease and controlling symptoms. Paradoxically, however, treatment with TNFα inhibitors can either have no clinical effects, or even exacerbate disease in some patients. The explanation for such contradictory outcomes may lay in how and which downstream signalling pathways are activated and drive disease...
September 14, 2016: Cytokine
https://www.readbyqxmd.com/read/27639807/rectal-delivery-of-a-dnazyme-that-specifically-blocks-the-transcription-factor-gata3-and-reduces-colitis-in-mice
#14
Vanessa Popp, Katharina Gerlach, Stefanie Mott, Agnieszka Turowska, Holger Garn, Raja Atreya, Hans-Anton Lehr, I-Cheng Ho, Harald Renz, Benno Weigmann, Markus F Neurath
BACKGROUND & AIMS: GATA3 is a transcription factor that regulates T-cell production of cytokines. We investigated the role of GATA3 in development of colitis in mice. METHODS: We performed quantitative polymerase chain reaction and immunofluorescence analyses of colon tissues from patients with Crohn's disease (n = 61) or ulcerative colitis (UC, n = 74) or from patients without inflammatory bowel diseases (n = 22), to measure levels of GATA3. Colitis was induced by administration of oxazolone or 2,4,6-trinitrobenzenesulfonic acid to control mice, mice with T-cell-specific deletion of GATA3, and mice with deletion of tumor necrosis factor receptor (TNFR) 1 and TNFR2 (TNFR double knockouts); some mice were given a GATA3-specific DNAzyme (hgd40) or a control DNAzyme via intrarectal administration, or systemic injections of an antibody to TNF before or during sensitization and challenge phase of colitis induction...
September 14, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27626702/phenotypic-screening-reveals-tnfr2-as-a-promising-target-for-cancer-immunotherapy
#15
Geoffrey S Williams, Bina Mistry, Sandrine Guillard, Jane Coates Ulrichsen, Alan M Sandercock, Jun Wang, Andrea González-Muñoz, Julie Parmentier, Chelsea Black, Jo Soden, Jim Freeth, Jelena Jovanović, Rebecca Leyland, Rafia S Al-Lamki, Andrew J Leishman, Steven J Rust, Ross Stewart, Lutz Jermutus, John R Bradley, Vahe Bedian, Viia Valge-Archer, Ralph Minter, Robert W Wilkinson
Antibodies that target cell-surface molecules on T cells can enhance anti-tumor immune responses, resulting in sustained immune-mediated control of cancer. We set out to find new cancer immunotherapy targets by phenotypic screening on human regulatory T (Treg) cells and report the discovery of novel activators of tumor necrosis factor receptor 2 (TNFR2) and a potential role for this target in immunotherapy. A diverse phage display library was screened to find antibody mimetics with preferential binding to Treg cells, the most Treg-selective of which were all, without exception, found to bind specifically to TNFR2...
September 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27620818/identification-and-functional-characterization-of-tumor-necrosis-factor-receptor-1-tnfr1-of-grass-carp-ctenopharyngodon-idella
#16
Shengnan Zhang, Rui Zhang, Tengyue Ma, Xingyang Qiu, Xinyan Wang, Anying Zhang, Hong Zhou
Tumor necrosis factor-alpha (TNF-α) exerts its regulatory effects by binding one of two TNF receptors, TNF-α receptor 1 (TNFR1) or TNFR2. In this study, we isolated and identified the cDNA sequence of grass carp TNFR1 (gcTNFR1). Similar to its homologs in other fish species, the putative protein of gcTNFR1 possessed an extracellular region containing three TNF homology domains, a transmembrane region and a cytoplasmic region with a conserved death domain. Consistent with the widespread expression of mammalian TNFR1, gcTNFR1 transcripts ubiquitously expressed in spleen, thymus, liver, heart, gill, intestine, brain and head kidney with the highest expression levels in head kidney...
September 9, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27612997/hyperoxaluria-requires-tnf-receptors-to-initiate-crystal-adhesion-and-kidney-stone-disease
#17
Shrikant R Mulay, Jonathan N Eberhard, Jyaysi Desai, Julian A Marschner, Santhosh V R Kumar, Marc Weidenbusch, Melissa Grigorescu, Maciej Lech, Nuru Eltrich, Lisa Müller, Wolfgang Hans, Martin Hrabě de Angelis, Volker Vielhauer, Bernd Hoppe, John Asplin, Nicolai Burzlaff, Martin Herrmann, Andrew Evan, Hans-Joachim Anders
Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data...
September 9, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27601345/tnfr2-expression-by-cd4-effector-t-cells-is-required-to-induce-full-fledged-experimental-colitis
#18
Xin Chen, Yingjie Nie, Haitao Xiao, Zhaoxiang Bian, Anthony J Scarzello, Na-Young Song, Trivett L Anna, De Yang, Joost J Oppenheim
There is now compelling evidence that TNFR2 is constitutively expressed on CD4(+) Foxp3(+) regulatory T cells (Tregs) and TNF-TNFR2 interaction is critical for the activation, expansion and functional stability of Tregs. However, we showed that the expression of TNFR2 was also up-regulated on CD4(+) Foxp3(-) effector T cells (Teffs) upon TCR stimulation. In order to define the role of TNFR2 in the pathogenic CD4 T cells, we compared the effect of transferred naïve CD4 cells from WT mice and TNFR2(-/-) mice into Rag 1(-/-) recipients...
September 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27591224/tnf-receptor-signaling-inhibits-cardiomyogenic-differentiation-of-cardiac-stem-cells-and-promotes-a-neuroadrenergic-like-fate
#19
Tariq Hamid, Yuanyuan Xu, Mohamed Ameen Ismahil, Qianhong Li, Steven P Jones, Aruni Bhatnagar, Roberto Bolli, Sumanth D Prabhu
Despite expansion of resident cardiac stem cells (CSCs; c-kit(+)Lin(-)) after myocardial infarction, endogenous repair processes are insufficient to prevent adverse cardiac remodeling and heart failure (HF). This suggests that the microenvironment in post-ischemic and failing hearts compromises CSC regenerative potential. Inflammatory cytokines, such as tumor necrosis factor-α (TNF), are increased after infarction and in HF; whether they modulate CSC function is unknown. As the effects of TNF are specific to its two receptors (TNFRs), we tested the hypothesis that TNF differentially modulates CSC function in a TNFR-specific manner...
November 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27591086/microrna148b-3p-inhibits-mtorc1-dependent-apoptosis-in-diabetes-by-repressing-tnfr2-in-proximal-tubular-cells
#20
Shogo Kuwagata, Shinji Kume, Masami Chin-Kanasaki, Hisazumi Araki, Shinichi Araki, Jun Nakazawa, Takeshi Sugaya, Daisuke Koya, Masakazu Haneda, Hiroshi Maegawa, Takashi Uzu
Hypoxia causes proximal tubular cell damage in diabetes, even though proximal tubular cells have an adaptive system to combat hypoxia involving induction of hypoxia factor-1 (HIF-1) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). Here, we examined the interference effect of altered glucose and lipid metabolism on the hypoxia responses in proximal tubular cells. In culture, hypoxia alone induced HIF-1 and inhibited mTORC1, preventing death in proximal tubular cells. However, hypoxia with high glucose and palmitate increased mTORC1 activity and promoted apoptosis in proximal tubular cells, which was inhibited by pharmacological and genetic inactivation of mTORC1...
August 30, 2016: Kidney International
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