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https://www.readbyqxmd.com/read/28723598/effects-of-tumor-necrosis-factor-blocker-on-salicylate-induced-tinnitus-in-mice
#1
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
#2
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
#3
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
#4
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...
June 30, 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
#5
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 pro-inflammatory and pro-apoptotic effects, tumor necrosis factor α (TNFα) can, under certain circumstances, promote improvements in mitochondrial integrity and function, phenomena that can be ascribed to the existence of TNFα receptor 2 (TNFR2). Objective: The present study aimed to investigate whether and how TNFR2 activation mediates the effects of TNFα on mitochondria...
June 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28620393/tweak-fn14-activation-participates-in-ro52-mediated-photosensitization-in-cutaneous-lupus-erythematosus
#6
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
#7
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
#8
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
#9
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/blockade-of-the-dissociation-of-nmmhc-iia-from-tnfr2-by-d39-a-saponin-from-liriope-muscari-suppresses-tissue-factor-expression-and-venous-thrombosis
#10
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) has been demonstrated to play a key role in tissue factor (TF) expression and venous thrombosis. However, whether natural products could inhibit thrombosis via NMMHC IIA remains unclear. In this study, we identified that a representative natural saponin D39 from Liriope muscari showed anti-thrombotic activity by targeting NMMHC IIA. EXPERIMENTAL APPROACH: TF expression and activity in endothelial cells were analysed in vitro by western blot and simplified chromogenic assays...
May 26, 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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28497109/hippocampal-tnf%C3%AE-signaling-contributes-to-seizure-generation-in-an-infection-induced-mouse-model-of-limbic-epilepsy
#14
Dipan C Patel, Glenna Wallis, E Jill Dahle, Pallavi B McElroy, Kyle E Thomson, Raymond J Tesi, David E Szymkowski, Peter J West, Roy M Smeal, Manisha Patel, Robert S Fujinami, H Steve White, Karen S Wilcox
Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler's murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28476889/structure-of-the-human-aminopeptidase-xpnpep3-and-comparison-of-its-in-vitro-activity-with-icp55-orthologs-insights-into-diverse-cellular-processes
#15
COMPARATIVE STUDY
Rahul Singh, Sahayog N Jamdar, Venuka Durani Goyal, Ashwani Kumar, Biplab Ghosh, Ravindra D Makde
The human aminopeptidase XPNPEP3 is associated with cystic kidney disease and TNF-TNFR2 cellular signaling. Its yeast and plant homolog Icp55 processes several imported mitochondrial matrix proteins leading to their stabilization. However, the molecular basis for the diverse roles of these enzymes in the cell is unknown. Here, we report the crystal structure of human XPNPEP3 with bound apstatin product at 1.65 Å resolution, and we compare its in vitro substrate specificity with those of fungal Icp55 enzymes...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28476134/overexpression-of-rkip-and-its-cross-talk-with-several-regulatory-gene-products-in-multiple-myeloma
#16
REVIEW
Anna Shvartsur, Kevin B Givechian, Hermes Garban, Benjamin Bonavida
Multiple myeloma (MM) is a clonal plasma-cell neoplastic disorder arising from an indolent premalignant disease known as monoclonal gammopathy of undetermined significance (MGUS). MM is a biologically complex heterogeneous disease reflected by its variable clinical responses of patients receiving the same treatment. Therefore, a molecular identification of stage-specific biomarkers will support a more individualized precise diagnostic/prognostic approach, an effective therapeutic regime, and will assist in the identification of novel therapeutic molecular targets...
May 5, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28454880/expression-of-negative-immune-regulatory-molecules-pro-inflammatory-chemokine-and-cytokines-in-immunopathology-of-ecm-developing-mice
#17
Ashwin V Khandare, Deepali Bobade, Mangesh Deval, Tushar Patil, Bhaskar Saha, D Prakash
The pathological events in human cerebral malaria are mimicked in the experimental cerebral malaria (ECM) in Plasmodium berghei ANKA (PBA)-infected C57BL/6 mice. Although previously implied in ECM, the kinetics of cytokines and chemokines expression-an essential functional feature for defining causality in ECM development-remained untested. Herein, we characterized the immunopathological changes and the expression of negative immune regulatory molecules, cytokines and chemokines through asymptomatic (3days after infection, 3dpi), symptomatic (5dpi) and ECM (7dpi) stages in PBA-infected C57BL/6 mice...
April 25, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28451639/microglial-tnf%C3%AE-induces-cox2-and-pgi2-synthase-expression-in-spinal-endothelial-cells-during-neuropathic-pain
#18
Hirosato Kanda, Kimiko Kobayashi, Hiroki Yamanaka, Masamichi Okubo, Koichi Noguchi
Prostaglandins (PGs) are typical lipid mediators that play a role in homeostasis and disease. They are synthesized from arachidonic acid by cyclooxygenase 1 (COX1) and COX2. Although COX2 has been reported to be upregulated in the spinal cord after nerve injury, its expression and functional roles in neuropathic pain remain unclear. In this study, we investigated the expression of Cox2, PGI2 synthase (Pgis), and prostaglandin I2 receptor (IP receptor) mRNA in the rat spinal cord after spared nerve injury (SNI)...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28412748/tumor-necrosis-factor-receptor-2-akt-and-erk-signaling-pathways-contribute-to-the-switch-from-fibroblasts-to-cafs-by-progranulin-in-microenvironment-of-colorectal-cancer
#19
Linlin Wang, Dong Yang, Jing Tian, Aiqin Gao, Yihang Shen, Xia Ren, Xia Li, Guosheng Jiang, Taotao Dong
Cancer associated fibroblasts (CAFs) are a crucial cellular component in tumor microenvironment and could promote tumor progression. CAFs are usually derived from resident fibroblasts, which undergoing an activated process stimulated by tumor cells. However, the agents and mechanism driving this switch have not yet been elucidated. Progranulin (PGRN), a well acknowledged secreted glycoprotein, could promote proliferation and angiogenesis of colorectal cancer (CRC) cells, and high expression of PGRN correlated with patient poor prognosis...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410596/toll-like-receptor-4-in-glial-inflammatory-responses-to-air-pollution-in-vitro-and-in-vivo
#20
Nicholas C Woodward, Morgan C Levine, Amin Haghani, Farimah Shirmohammadi, Arian Saffari, Constantinos Sioutas, Todd E Morgan, Caleb E Finch
BACKGROUND: Exposure to traffic-related air pollution (TRAP) is associated with accelerated cognitive aging and higher dementia risk in human populations. Rodent brains respond to TRAP with activation of astrocytes and microglia, increased inflammatory cytokines, and neurite atrophy. A role for Toll-like receptor 4 (TLR4) was suggested in mouse TLR4-knockouts, which had attenuated lung macrophage responses to air pollution. METHODS: To further analyze these mechanisms, we examined mixed glial cultures (astrocytes and microglia) for RNA responses to nanoscale particulate matter (nPM; diameter <0...
April 14, 2017: Journal of Neuroinflammation
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