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https://www.readbyqxmd.com/read/28801579/tnf%C3%AE-induced-up-regulation-of-na-k-2cl-cotransporter-nkcc1-in-hepatic-ammonia-clearance-and-cerebral-ammonia-toxicity
#1
Vitaly I Pozdeev, Elisabeth Lang, Boris Görg, Hans J Bidmon, Prashant V Shinde, Gerald Kircheis, Diran Herebian, Klaus Pfeffer, Florian Lang, Dieter Häussinger, Karl S Lang, Philipp A Lang
The devastating consequences of hepatic failure include hepatic encephalopathy, a severe, life threatening impairment of neuronal function. Hepatic encephalopathy is caused by impaired hepatic clearance of NH4(+). Cellular NH4(+) uptake is accomplished mainly by the Na(+),K(+),2Cl(-) cotransporter. Here we show that hepatic clearance of NH4(+) is impaired in TNFα deficient as well as TNFR1&TNFR2 double knockout mice, which both develop hyperammonemia. Despite impaired hepatic clearance of NH4(+), TNFα deficient mice and TNFR1 deficient mice were protected against acute ammonia intoxication...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761107/regulatory-t-cells-from-pancreatic-lymphnodes-of-patients-with-type-1-diabetes-express-increased-levels-of-microrna-mir-125a-5p-that-limits-ccr2-expression
#2
Guido Sebastiani, Giuliana Ventriglia, Angela Stabilini, Carlo Socci, Cristina Morsiani, Andrea Laurenzi, Laura Nigi, Caterina Formichi, Bechara Mfarrej, Alessandra Petrelli, Georgia Fousteri, Todd M Brusko, Francesco Dotta, Manuela Battaglia
Autoimmune type 1 diabetes (T1D) is thought to be caused by a defective immune regulation with regulatory T (Treg) cells playing a fundamental role in this process. Tolerance mechanisms depend on tunable responses that are sensitive to minor perturbations in the expression of molecules that can be carried out by multiple epigenetic mechanisms, including regulation by microRNAs. In this study, microRNA expression profile was investigated in Treg cells isolated from peripheral blood (PB) and from pancreatic draining lymph nodes (PLN) of T1D patients and non-diabetic subjects...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747780/novel-strategies-to-mimic-transmembrane-tumor-necrosis-factor-dependent-activation-of-tumor-necrosis-factor-receptor-2
#3
Roman Fischer, Jessica Marsal, Cristiano Guttà, Stephan A Eisler, Nathalie Peters, John R Bethea, Klaus Pfizenmaier, Roland E Kontermann
Tumor necrosis factor receptor 2 (TNFR2) is known to mediate immune suppression and tissue regeneration. Interestingly, the transmembrane form of tumor necrosis factor (tmTNF) is necessary to robustly activate TNFR2. To characterize the stoichiometry and composition of tmTNF during TNFR2 activation, we constructed differently oligomerized single chain TNF ligands (scTNF) comprised of three TNF homology domain (THD) protomers that mimic tmTNF. Using a variety of cellular and in vivo assays, we can show that higher oligomerization of the scTNF trimers results in more efficient TNF/TNFR2 clustering and subsequent signal transduction...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746777/functionality-of-intrinsic-disorder-in-tumor-necrosis-factor-%C3%AE-and-its-receptors
#4
Vladimir N Uversky, Nawal Abd El-Baky, Esmail M El-Fakharany, Amira Sabry, Ehab H Mattar, Alexey V Uversky, Elrashdy M Redwan
Tumor necrosis factor-α (TNF-α) is a pleiotropic inflammatory cytokine that exerts potent cytotoxic effects on solid tumor cells, while not affecting their normal counterparts. It is also known that TNF-α exerts many of its biological functions via interaction with specific receptors. To understand the potential roles of intrinsic disorder in the functioning of this important cytokine, we explored the peculiarities of intrinsic disorder distribution in human TNF-α and its homologues from various species, ranging from zebrafish to chimpanzee...
July 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28744116/tumor-necrosis-factor-receptor-2-as-a-possible-marker-of-copd-in-smokers-and-ex-smokers
#5
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/28736792/double-injected-human-stem-cells-enhance-rehabilitation-in-tbi-mice-via-modulation-of-survival-and-inflammation
#6
Chul Kim, Ji-Min Park, TaeHo Kong, Seungmin Lee, Ki-Weon Seo, Yuri Choi, Young Sook Song, Jisook Moon
Traumatic brain injury (TBI), a complicated form of brain damage, is a major cause of mortality in adults. Following mechanical and structural primary insults, a battery of secondary insults, including neurotransmitter-mediated cytotoxicity, dysregulation of calcium and macromolecule homeostasis, and increased oxidative stress, exacerbate brain injury and functional deficits. Although stem cell therapy is considered to be an alternative treatment for brain injuries, such as TBI and stroke, many obstacles remain...
July 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28733556/transmembrane-tnf-%C3%AE-promotes-activation-induced-cell-death-by-forward-and-reverse-signaling
#7
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/28723598/effects-of-tumor-necrosis-factor-blocker-on-salicylate-induced-tinnitus-in-mice
#8
Juen-Haur Hwang, David Chang-Wei Huang, Yin-Chang Lu, Wei-Shiung Yang, Tien-Chen Liu
OBJECTIVE: Neuroinflammation is considered a novel mechanism for acute tinnitus. Here, we investigated the effects of a tumor necrosis factor (TNF) blocker on the gene expression of inflammatory-cytokine in the cochlea in a tinnitus animal model. METHODS: Enbrel® (30 mg/kg, intraperitoneally (i.p.)) were administrated to the mice with the salicylate induced tinnitus for 3 days. Tinnitus score and mRNA expression levels of TNFR1, TNFR2, and N-methyl-d-aspartate receptor subunit 2B (NR2B) and its downstream regulatory element antagonist modulator (DREAM) in the cochlea of mice were measured and compared to the control...
June 1, 2017: International Tinnitus Journal
https://www.readbyqxmd.com/read/28723569/xiap-loss-triggers-ripk3-and-caspase-8-driven-il-1%C3%AE-activation-and-cell-death-as-a-consequence-of-tlr-myd88-induced-ciap1-traf2-degradation
#9
Kate E Lawlor, Rebecca Feltham, Monica Yabal, Stephanie A Conos, Kaiwen W Chen, Stephanie Ziehe, Carina Graß, Yifan Zhan, Tan A Nguyen, Cathrine Hall, Angelina J Vince, Simon M Chatfield, Damian B D'Silva, Kenneth C Pang, Kate Schroder, John Silke, David L Vaux, Philipp J Jost, James E Vince
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28702675/tnf-%C3%AE-genetic-predisposition-and-higher-expression-of-inflammatory-pathway-components-in-keratoconus
#10
Muneeza Arbab, Saira Tahir, Muhammad Khizar Niazi, Mazhar Ishaq, Alamdar Hussain, Pir Muhammad Siddique, Sadia Saeed, Wajid Ali Khan, Raheel Qamar, Azeem Mehmood Butt, Maleeha Azam
Purpose: To date keratoconus (KC) pathogenesis is undefined; however, the involvement of inflammatory pathways in disease development is becoming apparent. In the present study, we investigated the role of a promoter region polymorphism rs1800629 (-308G>A) in the inflammatory pathway component TNF-α and its effects on the expression of TNF-α and downstream molecules tumor necrosis factor receptor 1 and 2 (TNFR1 and TNFR2), v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), and interleukin 6 (IL-6) in KC development...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28677724/tnfr2-promotes-adriamycin-resistance-in-breast-cancer-cells-by-repairing-dna-damage
#11
Fuqian Yang, Nana Zhao, Nan Wu
In recent years, tumor necrosis factor receptor 2 (TNFR2) has attracted increasing attention for its important roles in promoting proliferation, migration and angiogenesis in several types of cancer. However, its role in drug resistance remain unclear. In the present study, TNFR2 expression levels in MDA‑MB‑231 and MCF‑7 breast cancer cells were demonstrated to be associated with Adriamycin (ADM) resistance. Silencing of TNFR2 in MCF‑7 cells significantly inhibited ADM resistance, while overexpression of TNFR2 in MDA‑MB‑231 cells significantly enhanced ADM resistance...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28637784/tnfr2-stimulation-promotes-mitochondrial-fusion-via-stat3-and-nf-kb-dependent-activation-of-opa1-expression
#12
Jinliang Nan, Hengxun Hu, Yong Sun, Lianlian Zhu, Yingchao Wang, Zhiwei Zhong, Jing Zhao, Na Zhang, Ya Wang, Yaping Wang, Jian Ye, Ling Zhang, Xinyang Hu, Wei Zhu, Jian'an Wang
RATIONALE: Mitochondria are important cellular organelles and play essential roles in maintaining cell structure and function. Emerging evidence indicates that in addition to having proinflammatory and proapoptotic effects, TNFα (tumor necrosis factor α) can, under certain circumstances, promote improvements in mitochondrial integrity and function, phenomena that can be ascribed to the existence of TNFR2 (TNFα receptor 2). OBJECTIVE: The present study aimed to investigate whether and how TNFR2 activation mediates the effects of TNFα on mitochondria...
August 4, 2017: Circulation Research
https://www.readbyqxmd.com/read/28620393/tweak-fn14-activation-participates-in-ro52-mediated-photosensitization-in-cutaneous-lupus-erythematosus
#13
Yale Liu, Meifeng Xu, Xiaoyun Min, Kunyi Wu, Ting Zhang, Ke Li, Shengxiang Xiao, Yumin Xia
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) binds to its sole receptor fibroblast growth factor-inducible 14 (Fn14), participating in various inflammatory responses. Recently, TWEAK/Fn14 activation was found prominent in the lesions of cutaneous lupus erythematosus (CLE). This study was designed to further reveal the potential role of this pathway in Ro52-mediated photosensitization. TWEAK, Fn14, and Ro52 were determined in the skin lesions of patients with CLE. Murine keratinocytes received ultraviolet B (UVB) irradiation or plus TWEAK stimulation and underwent detection for Ro52 and proinflammatory cytokines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28619762/impaired-tnf-tnfr2-signaling-enhances-th2-and-th17-polarization-and-aggravates-allergic-airway-inflammation
#14
Xiao-Ming Li, Xi Chen, Wen Gu, Yi-Jia Guo, Yi Cheng, Juan Peng, Xue-Jun Guo
CD4+T cell differentiation plays an important role in allergic airway diseases. Tumor necrosis factor receptor 2 (TNFR2) has been shown to regulate CD4+T lymphocyte differentiation, but its role in allergic airway inflammation is not clear. Here we investigated the role of TNFR2 in allergic airway inflammation. Mouse model was generated by immunization with OVA and intranasal administration of TNFR2 antibody. Airway inflammation and CD4+T cell differentiation were measured in vivo and in vitro. Inhibited TNFR2 signaling aggravated airway inflammation and increased the expression of inflammatory cytokines (IL-4, IL-5, IL-17, and TNF-α) in serum and bronchoalveolar lavage fluid (BALF)...
June 15, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28601149/cells-expressing-cd4-cd8-mhcii-and-endoglin-in-the-canine-corpus-luteum-of-pregnancy-and-prepartum-activation-of-the-luteal-tnf%C3%AE-system
#15
Renata M Nowaczyk, Ewelina Jursza-Piotrowska, Aykut Gram, Marta J Siemieniuch, Alois Boos, Mariusz P Kowalewski
In the dog, knowledge about involvement of the immune system in controlling luteal function is restricted to observations showing a time-dependent invasion of immune cells into the corpus luteum (CL) of non-pregnant bitches. Therefore, this study investigated the presence of CD4-, CD8-, MHCII- and endoglin-expressing cells in CL collected throughout pregnancy from pre-implantation until prepartum luteolysis. Immunohistochemistry and semi-quantitative RT-PCR were applied. The time-dependent expression of CD4, CD8 and endoglin was more strongly related to formation of the CL, whereas MHCII was induced during luteolysis...
August 2017: Theriogenology
https://www.readbyqxmd.com/read/28600151/splenomegaly-myeloid-lineage-expansion-and-increased-osteoclastogenesis-in-osteogenesis-imperfecta-murine
#16
Brya G Matthews, Emilie Roeder, Xi Wang, Hector Leonardo Aguila, Sun-Kyeong Lee, Danka Grcevic, Ivo Kalajzic
Osteogenesis imperfecta (OI) is a disease caused by defects in type I collagen production that results in brittle bones. While the pathology is mainly caused by defects in the osteoblast lineage, there is also elevated bone resorption by osteoclasts resulting in high bone turnover in severe forms of the disease. Osteoclasts originate from hematopoietic myeloid cells, however changes in hematopoiesis have not been previously documented in OI. In this study, we evaluated hematopoietic lineage distribution and osteoclast progenitor cell frequency in bone marrow, spleen and peripheral blood of osteogenesis imperfecta murine (OIM) mice, a model of severe OI...
June 7, 2017: Bone
https://www.readbyqxmd.com/read/28547925/the-saponin-d39-blocks-dissociation-of-non-muscular-myosin-heavy-chain-iia-from-tnf-receptor-2-suppressing-tissue-factor-expression-and-venous-thrombosis
#17
Ke-Feng Zhai, Jin-Rong Zheng, You-Mei Tang, Fang Li, Yan-Ni Lv, Yuan-Yuan Zhang, Zhen Gao, Jin Qi, Bo-Yang Yu, Jun-Ping Kou
BACKGROUND AND PURPOSE: Non-muscular myosin heavy chain IIA (NMMHC IIA) plays a key role in tissue factor expression and venous thrombosis. Natural products might inhibit thrombosis through effects on NMMHC IIA. Here, we have shown that a natural saponin, D39, from Liriope muscari exerted anti-thrombotic activity in vivo, by targeting NMMHC IIA. EXPERIMENTAL APPROACH: Expression and activity of tissue factor in endothelial cells were analysed in vitro by Western blot and simplified chromogenic assays...
September 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28542390/analysis-of-early-mesothelial-cell-responses-to-staphylococcus-epidermidis-isolated-from-patients-with-peritoneal-dialysis-associated-peritonitis
#18
Amanda L McGuire, Kieran T Mulroney, Christine F Carson, Ramesh Ram, Grant Morahan, Aron Chakera
The major complication of peritoneal dialysis (PD) is the development of peritonitis, an infection within the abdominal cavity, primarily caused by bacteria. PD peritonitis is associated with significant morbidity, mortality and health care costs. Staphylococcus epidermidis is the most frequently isolated cause of PD-associated peritonitis. Mesothelial cells are integral to the host response to peritonitis, and subsequent clinical outcomes, yet the effects of infection on mesothelial cells are not well characterised...
2017: PloS One
https://www.readbyqxmd.com/read/28542350/t0001-a-variant-of-tnfr2-fc-fusion-protein-exhibits-improved-fc-effector-functions-through-increased-binding-to-membrane-bound-tnf%C3%AE
#19
Yijun Shen, Gang Li, Chunying Gu, Ben Chen, Aihua Chen, Hua Li, Bei Gao, Chencai Liang, Jingsong Wu, Tong Yang, Li Jin, Yong Su
T0001 is a recombinant human TNFR-Fc fusion protein mutant; it exhibits higher affinity to TNFα than etanercept and is now being tested in a Phase 1 study in China (ClinicalTrials.gov Identifier: NCT02481180). T0001 can inhibit the binding of soluble TNFα (sTNFα) or membrane-bound TNFα (mTNFα) to TNF receptors. When bound to mTNFα, the Fc-bearing TNFα antagonists have the potential to induce Fc-mediated effects, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) as well as outside-to-inside signals (apoptosis mainly)...
2017: PloS One
https://www.readbyqxmd.com/read/28511863/expression-of-tnf-%C3%AE-system-members-in-bovine-ovarian-follicles-and-the-effects-of-tnf-%C3%AE-or-dexamethasone-on-preantral-follicle-survival-development-and-ultrastructure-in-vitro
#20
A W B Silva, R P Ribeiro, V G Menezes, R S Barberino, J R S Passos, A M P Dau, J J N Costa, L R F Melo, F T G Bezerra, M A M Donato, C A Peixoto, M H T Matos, P B D Gonçalves, R van den Hurk, J R V Silva
This study was conducted to detect the protein expression of TNF-α system members (TNF-α/TNFR1/TNFR2) in bovine ovarian follicles and to evaluate the effects of TNF-α or dexamethasone on the survival and growth of primordial follicles in vitro, as well as on gene expression in cultured ovarian tissue. It was hypothesized that TNF-α induces follicular atresia in ovarian tissues cultured in vitro, and that dexamethasone suppresses the production of endogenous TNF-α, which can improve follicle viability in vitro...
May 6, 2017: Animal Reproduction Science
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