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https://www.readbyqxmd.com/read/28926524/prognostic-significance-of-tnfr-associated-factor-1-and-2-traf1-and-traf2-in-glioblastoma
#1
Wenqing Zhang, Ying Sun, Lei Liu, Zongpeng Li
BACKGROUND TNFR-associated factor 1 (TRAF1) and TRAF2 have been demonstrated to inhibit apoptosis and promote cell survival in glioblastoma (GBM) cells with experiments in vitro. However, their clinical and prognostic significance have not been elucidated. MATERIAL AND METHODS In our study, we for the first time investigated the expression of TRAF1 and TRAF2 in 105 GBM tissues. Furthermore, we evaluated their clinical significance, including their association with clinicopathologic factors and prognostic value...
September 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28912506/role-of-tumor-necrosis-factor-%C3%AE-and-its-receptors-in-diesel-exhaust-particle-induced-pulmonary-inflammation
#2
Smitha Kumar, Guy Joos, Louis Boon, Kurt Tournoy, Sharen Provoost, Tania Maes
Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung. However, the underlying mechanisms remain to be elucidated. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that operates by binding to tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2). The role of TNF-α signaling and the importance of either TNFR1 or TNFR2 in the DEP-induced inflammatory response has not yet been elucidated. TNF-α knockout (KO), TNFR1 KO, TNFR2 KO, TNFR1/TNFR2 double KO (TNFR-DKO) and wild type (WT) mice were intratracheally exposed to saline or DEP...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877989/regulatory-t-cell-mediated-suppression-of-inflammation-induced-by-dr3-signaling-is-dependent-on-galectin-9
#3
Shravan Madireddi, So-Young Eun, Amit K Mehta, Aruna Birta, Dirk M Zajonc, Toshiro Niki, Mitsuomi Hirashima, Eckhard R Podack, Taylor H Schreiber, Michael Croft
Stimulation of several TNF receptor family proteins has been shown to dampen inflammatory disease in murine models through augmenting the number and/or activity of regulatory T cells (Tregs). We recently found that one molecule, 4-1BB, used binding to Galectin-9 to exert its immunosuppressive effects and drive expansion of CD8(+)Foxp3(-) Tregs. We now show that ligation of another TNFR family molecule, DR3, which has previously been found to strongly expand CD4(+)Foxp3(+) Tregs and suppress inflammation, also requires Galectin-9...
September 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28875549/the-contribution-of-toll-like-receptor-signaling-to-the-development-of-liver-fibrosis-and-cancer-in-hepatocyte-specific-tak1-deleted-mice
#4
Isabelle Jingyi Song, Yoon Mee Yang, Sayaka Inokuchi-Shimizu, Yoon Seok Roh, Ling Yang, Ekihiro Seki
Hepatocyte death is associated with liver inflammation, fibrosis, and hepatocellular carcinoma (HCC). Damaged cells trigger inflammation through activation of Toll-like receptor (TLR). Although the role of TLR4 in HCC development has been reported, the role of TLR9 in the development of HCC remains elusive. To investigate the role of TLR4 and TLR9 signaling in liver inflammation-fibrosis-cancer axis, we took advantage of mice with hepatic deletion of transforming growth factor-β-activated kinase 1 (Tak1ΔHep) that develop spontaneous liver injury, inflammation, fibrosis, and HCC, recapitulating the pathology of human HCC...
September 5, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28864474/the-scaffolding-protein-iqgap1-interacts-with-nlrc3-and-inhibits-type-i-ifn-production
#5
Aaron M Tocker, Emily Durocher, Kimberly D Jacob, Kate E Trieschman, Suzanna M Talento, Alma A Rechnitzer, David M Roberts, Beckley K Davis
Sensing of cytosolic nucleotides is a critical initial step in the elaboration of type I IFN. One of several upstream receptors, cyclic GMP-AMP synthase, binds to cytosolic DNA and generates dicyclic nucleotides that act as secondary messengers. These secondary messengers bind directly to stimulator of IFN genes (STING). STING recruits TNFR-associated NF-κB kinase-binding kinase 1 which acts as a critical node that allows for efficient activation of IFN regulatory factors to drive the antiviral transcriptome...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28834692/soluble-extracellular-domain-of-death-receptor-5-inhibits-trail-induced-apoptosis-by-disrupting-receptor-receptor-interactions
#6
Nagamani Vunnam, Chih Hung Lo, Benjamin D Grant, David D Thomas, Jonathan N Sachs
Dysregulation of tumor necrosis factor receptor (TNFR) signaling is a key feature of various inflammatory disorders. Current treatments for TNF-related diseases function either by sequestering ligand or blocking ligand-receptor interactions, which can cause dangerous side effects by inhibiting the receptors that are not involved in the disease condition. Thus, alternate strategies that target receptor-receptor interactions are needed. We hypothesized that the soluble extracellular domain (ECD) of long isoform of Death Receptor 5 (DR5) could block endogenous receptor assembly, mimicking the biological effect of decoy receptors that lack the death domain to trigger apoptosis...
August 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28830973/tumor-necrosis-factor-receptor-1-and-2-are-associated-with-risk-of-intracerebral-hemorrhage
#7
Edith H Svensson, Martin Söderholm, Kasim Abul-Kasim, Gunnar Engström
BACKGROUND AND PURPOSE: Raised plasma concentrations of tumor necrosis factor receptors (TNFR) have been linked to arterial stiffness, cerebral microbleeds, and vascular events. The aim of this study was to investigate the association of circulating levels of TNFR1 and TNFR2 with risk for future intracerebral hemorrhage (ICH). METHODS: The population-based MDCS cohort (Malmö Diet and Cancer Study; n=28 449) was conducted in 1991 to 1996. A nested case-control study was performed in the MDCS, including 220 cases who experienced ICH during the follow-up period (mean age at inclusion 62 years, 48% men) and 244 matched controls...
August 22, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28821873/tnf-%C3%AE-induced-inflammation-stimulates-apolipoprotein-a4-via-activation-of-tnfr2-and-nf-%C3%AE%C2%BAb-signaling-in-kidney-tubular-cells
#8
Hyung Ho Lee, Young In Cho, Sook Young Kim, Young Eun Yoon, Kyung Sup Kim, Sung Joon Hong, Woong Kyu Han
Apo-A4 expression was increased in tissues from chronic kidney disease (CKD) patients compared to that in normal kidney tissue. We determined the association of apo-A4 and its regulatory signals following acute kidney injury and elucidated the effects of apo-A4 on cell signaling pathways related to kidney injury in vitro and in vivo. Tumor necrosis factor (TNF)-α, which causes inflammatory cell injury, induced significantly increased expression of apo-A4 protein levels, and these levels were related to pro-inflammatory acute kidney injury in human kidney cells...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817177/the-n-terminal-ubiquitin-associated-domain-of-cezanne-is-crucial-for-its-function-to-suppress-nf-%C3%AE%C2%BAb-pathway
#9
Yanxi Ji, Liu Cao, Lanyi Zeng, Zhen Zhang, Qiaoqiao Xiao, Penglin Guan, Shiyou Chen, Yu Chen, Min Wang, Deyin Guo
Cezanne, a deubiquitinating cysteine protease (DUB) belonging to A20 subgroup of ovarian tumor (OTU) protein superfamily, functions as a negative regulator of NF-κB to attenuate NF-κB activation and to restrain pro-inflammatory transcription in response to TNF receptor (TNFR) signaling. It is the first documented OTU DUB that preferably disassembles Lys11-linked polyubiquitin chains and has been shown to regulate multiple cellular events including immune signaling, cell survival and tumor progression. Previous studies showed that in response to TNF stimulation, Cezanne is recruited to the activated TNFR complex to suppress the build-up of polyubiquitinated RIP1 signal by removing Lys63 polyubiquitin from RIP1...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28794434/protective-role-of-cellular-prion-protein-against-tnf%C3%AE-mediated-inflammation-through-tace-%C3%AE-secretase
#10
Juliette Ezpeleta, François Boudet-Devaud, Mathéa Pietri, Anne Baudry, Vincent Baudouin, Aurélie Alleaume-Butaux, Nathalie Dagoneau, Odile Kellermann, Jean-Marie Launay, Benoit Schneider
Although cellular prion protein PrP(C) is well known for its implication in Transmissible Spongiform Encephalopathies, its functions remain elusive. Combining in vitro and in vivo approaches, we here show that PrP(C) displays the intrinsic capacity to protect neuronal cells from a pro-inflammatory TNFα noxious insult. Mechanistically, PrP(C) coupling to the NADPH oxidase-TACE α-secretase signaling pathway promotes TACE-mediated cleavage of transmembrane TNFα receptors (TNFRs) and the release of soluble TNFR, which limits the sensitivity of recipient cells to TNFα...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793310/reduced-internalization-of-tnf-%C3%A9-tnfr1-down-regulates-caspase-dependent-phagocytosis-induced-cell-death-picd-in-neonatal-monocytes
#11
Stephan Dreschers, Christian Gille, Martin Haas, Florence Seubert, Christopher Platen, Thorsten W Orlikowsky
Phagocytosis-induced cell death (PICD) is diminished in cord blood monocytes (CBMO) as compared to cells from adults (PBMO) due to differences in the CD95-pathway. This may support a prolonged pro-inflammatory response with sequels of sustained inflammation as seen in neonatal sepsis. Here we hypothesized that TNF-α mediated induction of apoptosis is impaired in CBMO due to differences in the TNFR1-dependent internalization. Monocytes were infected with Escherichia coli-GFP (E. coli-GFP). Monocyte phenotype, phagocytic activity, induction of apoptosis, and TNF-α/TNF-receptor (TNFR) -expression were analysed...
2017: PloS One
https://www.readbyqxmd.com/read/28789924/constitutive-interaction-between-4-1bb-and-4-1bbl-on-murine-lps-activated-bone-marrow-dendritic-cells-masks-detection-of-4-1bbl-by-tks-1-but-not-19h3-antibody
#12
Achire N Mbanwi, Gloria H Y Lin, Kuan Chung Wang, Tania H Watts
4-1BB is a TNFR family member associated with NF-κB mediated survival signaling. 4-1BB is widely expressed on activated cells of the immune system, including activated T cells, NK cells and dendritic cells. Its ligand, 4-1BBL, is transiently expressed on activated antigen presenting cells and at low levels on activated T cells. Although 4-1BBL-deficient mice clearly demonstrate a role for 4-1BBL in CD8 T cell responses to viruses such as influenza, 4-1BBL can be difficult to detect following infection of mice...
August 5, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28768663/effects-of-multiple-simulated-birth-traumas-on-urethral-continence-function-in-rats
#13
Satoru Yoshikawa, Yasuhiro Sumino, Joonbeom Kwon, Takahisa Suzuki, Takeya Kitta, Minoru Miyazato, Naoki Yoshimura
Multiple vaginal parities have been reported to be an important risk factor for stress urinary incontinence (SUI). Simulated birth trauma with single vaginal distention (VD) has been used to induce the SUI condition in animals; however, the effect of multiple simulated birth traumas on the urethral continence function has not been well characterized. Therefore, we examined the effects of multiple VDs on urethral functions in vivo and the changes in gene expressions of several molecules in the urethra using female SD rats, which were divided into 3 groups; sham, VD-1 (single VD), and VD-3 groups (3 times of VDs every 2 weeks)...
August 2, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28761167/functional-detection-of-tnf-receptor-family-members-by-affinity-labeled-ligands
#14
Yang Xu, Lingmo Chang, Anliang Huang, Xiaojun Liu, Xinyu Liu, Hong Zhou, Joshua G Liang, Peng Liang
Aberrant expression of TNF family of cytokines has been linked to human diseases, and biologics targeting their signaling have become the best selling drugs globally. However, functional detection with labeled ligands for accurate detection of TNFR family of receptor-expressing target tissues or cell types remains to be developed. Here we show that TNF receptor family members are heat-stable and can be recognized both in vitro and in vivo by their ligands labeled with alkaline phosphatase. Such an approach may be used in lieu of antibodies for the identification of the cell types involved in receptor signaling during disease onset and progression...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28758875/functional-optimization-of-agonistic-antibodies-to-ox40-receptor-with-novel-fc-mutations-to-promote-antibody-multimerization
#15
Di Zhang, Anthony A Armstrong, Susan H Tam, Stephen G McCarthy, Jinquan Luo, Gary L Gilliland, Mark L Chiu
Immunostimulatory receptors belonging to the tumor necrosis factor receptor (TNFR) superfamily are emerging as promising targets for cancer immunotherapies. To optimize the agonism of therapeutic antibodies to these receptors, Fc engineering of antibodies was applied to facilitate the clustering of cell surface TNFRs to activate downstream signaling pathways. One engineering strategy is to identify Fc mutations that facilitate antibody multimerization on the cell surface directly. From the analyses of the crystal packing of IgG1 structures, we identified a novel set of Fc mutations, T437R and K248E, that facilitated antibody multimerization upon binding to antigens on cell surface...
July 31, 2017: MAbs
https://www.readbyqxmd.com/read/28747340/epithelial-tnf-receptor-signaling-promotes-mucosal-repair-in-inflammatory-bowel-disease
#16
Emily M Bradford, Stacy H Ryu, Ajay Pal Singh, Goo Lee, Tatiana Goretsky, Preetika Sinh, David B Williams, Amber L Cloud, Elias Gounaris, Vihang Patel, Olivia F Lamping, Evan B Lynch, Mary Pat Moyer, Isabelle G De Plaen, David J Shealy, Guang-Yu Yang, Terrence A Barrett
TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/β-catenin-mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models. We hypothesized that TNF exerts beneficial effects on intestinal epithelial cell (IEC) responses to injury...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28744116/tumor-necrosis-factor-receptor-2-as-a-possible-marker-of-copd-in-smokers-and-ex-smokers
#17
Laura Miranda de Oliveira Caram, R Ferrari, D L Nogueira, Mrm Oliveira, F V Francisqueti, S E Tanni, C R Corrêa, I Godoy
INTRODUCTION: Oxidative stress and systemic inflammation are higher in smokers and patients with COPD; however, markers that may help differentiate between smokers and patients with COPD have not yet been identified. We hypothesized that tumor necrosis factor-alpha receptor (TNFR) and soluble form of the receptor for advanced glycation end products (sRAGE) can be indicators of COPD in asymptomatic patients. PATIENTS AND METHODS: We evaluated 32 smokers (smoking history >10 pack-years), 32 patients with mild/moderate COPD (smokers and ex-smokers), and 32 never smokers...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28736159/a-novel-ccr-2-tlr-2-triggered-signaling-in-murine-peritoneal-macrophages-intensifies-bacterial-staphylococcus-aureus-killing-by-reactive-oxygen-species-through-tnf-r1
#18
Ajeya Nandi, Biswadev Bishayi
Macrophages are remarkably versatile in their ability to recognize and respond to a wide range of stimuli by expressing a variety of surface and intracellular receptors and triggering multiple signal transduction pathways. The onset of microbial infection is primarily determined by the initial contacts made by the microbes with the host macrophages. Although there prevail a relationship between the chemokine receptor and Toll like receptors during disease, particularly TLR-2 and CCR-2 signaling interdependence on each other has not been yet investigated during acute staphylococcal infection...
July 20, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28733556/transmembrane-tnf-%C3%AE-promotes-activation-induced-cell-death-by-forward-and-reverse-signaling
#19
Meng Zhang, Jing Wang, Lingwei Jia, Jin Huang, Cheng He, Fuqing Hu, Lifei Yuan, Guihua Wang, Mingxia Yu, Zhuoya Li
Secretory tumor necrosis factor-alpha (sTNF-α) is known to mediate activation- induced cell death (AICD). However, the role of tmTNF-α in AICD is still obscure. Here, we demonstrated that tmTNF-α expression significantly increased accompanied with enhanced apoptosis during AICD in Jurkat and primary human T cells. Knockdown or enhancement of tmTNF-α expression in activated T cells suppressed or promoted AICD, respectively. Treatment of activated T cells with exogenous tmTNF-α significantly augmented AICD, indicating that tmTNF-α as an effector molecule mediates AICD...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730425/at-101-acts-as-anti-proliferative-and-hormone-suppressive-agent-in-mouse-pituitary-corticotroph-tumor-cells
#20
B S Yurekli, B Karaca, A Kisim, E Bozkurt, H Atmaca, S Cetinkalp, G Ozgen, C Yilmaz, S Uzunoglu, R Uslu, F Saygili
PURPOSE: Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (-)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing's disease still remains a challenge for the clinicians...
July 20, 2017: Journal of Endocrinological Investigation
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