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TNFR2

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https://www.readbyqxmd.com/read/29295954/blockade-of-tnfr2-signaling-enhances-the-immunotherapeutic-effect-of-cpg-odn-in-a-mouse-model-of-colon-cancer
#1
Yingjie Nie, Jiang He, Hidekazu Shirota, Anna L Trivett, De Yang, Dennis M Klinman, Joost J Oppenheim, Xin Chen
Through the tumor necrosis factor (TNF) receptor type II (TNFR2), TNF preferentially activates, expands, and promotes the phenotypic stability of CD4+Foxp3+ regulatory T (Treg) cells. Those Treg cells that have a high abundance of TNFR2 have the maximal immunosuppressive capacity. We investigated whether targeting TNFR2 could effectively suppress the activity of Treg cells and consequently enhance the efficacy of cancer immunotherapy. We found that, relative to a suboptimal dose of the immunostimulatory Toll-like receptor 9 ligand CpG oligodeoxynucleotide (ODN), the combination of the suboptimal dose of CpG ODN with the TNFR2-blocking antibody M861 more markedly inhibited the growth of subcutaneously grafted mouse CT26 colon tumor cells...
January 2, 2018: Science Signaling
https://www.readbyqxmd.com/read/29273047/donepezil-suppresses-intracellular-ca2-mobilization-through-the-pi3k-pathway-in-rodent-microglia
#2
Yoshinori Haraguchi, Yoshito Mizoguchi, Masahiro Ohgidani, Yoshiomi Imamura, Toru Murakawa-Hirachi, Hiromi Nabeta, Hiroshi Tateishi, Takahiro A Kato, Akira Monji
BACKGROUND: Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer's disease (AD) is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Ca2+ mobilization in microglial cells...
December 22, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29258611/progranulin-derivative-atsttrin-protects-against-early-osteoarthritis-in-mouse-and-rat-models
#3
Jian-Lu Wei, Wenyu Fu, Yuan-Jing Ding, Aubryanna Hettinghouse, Matin Lendhey, Ran Schwarzkopf, Oran D Kennedy, Chuan-Ju Liu
BACKGROUND: Atsttrin, an engineered protein composed of three tumor necrosis factor receptor (TNFR)-binding fragments of progranulin (PGRN), shows therapeutic effect in multiple murine models of inflammatory arthritis . Additionally, intra-articular delivery of PGRN protects against osteoarthritis (OA) progression. The purpose of this study is to determine whether Atsttrin also has therapeutic effects in OA and the molecular mechanisms involved. METHODS: Surgically induced and noninvasive rupture OA models were established in mouse and rat, respectively...
December 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29248493/tnfaip3-a20-acts-as-master-switch-in-tnf%C3%AE-blockade-driven-il-17a-expression
#4
Paulo Cm Urbano, Raúl Aguirre-Gamboa, Angel Ashikov, Bennie van Heeswijk, Anja Krippner-Heidenreich, Henk Tijssen, Yang Li, Valderilio F Azevedo, Lisa Jt Smits, Frank Hoentjen, Irma Joosten, Hans Jpm Koenen
BACKGROUND: Anti-TNF inhibitors successfully improve life quality of patients suffering from inflammatory disease. Unfortunately, not all patients respond to anti-TNF therapy and some patients show paradoxical immune side-effects, which is poorly understood. Surprisingly, anti-TNF agents were shown to promote IL-17A production, with as yet unknown clinical implications. OBJECTIVE: To investigate the molecular mechanism underlying anti-TNF driven IL-17A expression and the clinical implications of this phenomenon...
December 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29237775/induction-of-immunosuppressive-cd8-cd25-foxp3-regulatory-t-cells-by-suboptimal-stimulation-with-staphylococcal-enterotoxin-c1
#5
Juyeun Lee, Nogi Park, Joo Youn Park, Barbara L F Kaplan, Stephen B Pruett, Juw Won Park, Yong Ho Park, Keun Seok Seo
Superantigens (SAgs) produced by Staphylococcus aureus at high concentrations induce proliferation of T cells bearing specific TCR Vβ sequences and massive cytokinemia that cause toxic shock syndrome. However, the biological relevance of SAgs produced at very low concentrations during asymptomatic colonization or chronic infections is not understood. In this study, we demonstrate that suboptimal stimulation of human PBMCs with a low concentration (1 ng/ml) of staphylococcal enterotoxin C1, at which half-maximal T cell proliferation was observed, induced CD8+CD25+ T cells expressing markers related to regulatory T cells (Tregs), such as IFN-γ, IL-10, TGF-β, FOXP3, CD28, CTLA4, TNFR2, CD45RO, and HLA-DR...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29234328/forward-and-reverse-signaling-mediated-by-transmembrane-tumor-necrosis-factor-alpha-and-tnf-receptor-2-potential-roles-in-an-immunosuppressive-tumor-microenvironment
#6
REVIEW
Yang Qu, Gang Zhao, Hui Li
Tumor necrosis factor-alpha (TNF-α) is a pleiotropic inflammatory cytokine produced mainly by activated macrophages, lymphocytes and other cell types. Two distinct forms of TNF-α have been identified: soluble TNF-α (sTNF-α) and transmembrane TNF-α (mTNF-α). mTNF-α, which is the precursor of sTNF-α, can be cleaved by the TNF-α converting enzyme (TACE) and is released as sTNF-α. sTNF-α binds primarily to TNF receptor 1 (TNFR1) and plays an important role in the inflammatory immune response, whereas mTNF-α interacts primarily with TNF receptor 2 (TNFR2) and mediates the promotion of cellular proliferation and survival and other biological effects...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29218573/dual-neutralization-of-tnfr-2-and-mmp-2-regulates-the-severity-of-s-aureus-induced-septic-arthritis-correlating-alteration-in-the-level-of-interferon-gamma-and-interleukin-10-in-terms-of-tnfr2-blocking
#7
Sahin Sultana, Rajen Dey, Biswadev Bishayi
Severity of S. aureus septic arthritis is correlated to prolonged inflammation by inflammatory cytokines like TNF-α, IL-1β, and IL-6 even after successful elimination of bacteria. Role of TNF-α via TNFR2 is not well established in this aspect. IFN-γ induces TNF-α release from the macrophages augmenting the inflammatory arthritis. IL-10 modulates the levels of pro-inflammatory cytokines promoting resolution of inflammation. TNF-α-TNFR2 signaling upregulates both of these cytokines. Higher level of MMP-2 induction by inflammatory cytokines during arthritis promotes tissue destruction...
December 7, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29212072/expression-of-tnf%C3%AE-receptors-on-immunocompetent-cells-is-increased-in-atopic-dermatitis
#8
Julia A Lopatnikova, Alina A Alshevskaya, Olga L Krugleeva, Vera M Nepomnyschih, Victor S Gladkikh, Vitaliy L Lukinov, Alexander V Karaulov, Sergey Vitalievich Sennikov
BACKGROUND: Expression levels of cytokine and growth factor receptors have been found to be important in the regulation of their action. Tumor necrosis factor-α (TNFα) is actively involved in inflammation processes in atopic dermatitis (AD), but the role of TNFα membrane receptors (TNFR) and their regulatory function in AD remains unclear. AIM: We aimed to determine the associations of parameters of TNFRα expression on immunocompetent cells with disease severity before and after therapy in AD patients...
2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29202842/preclinical-and-clinical-aspects-of-tnf-%C3%AE-and-its-receptors-tnfr1-and-tnfr2-in-breast-cancer
#9
REVIEW
Isela Martínez-Reza, Lorenza Díaz, Rocío García-Becerra
Breast cancer is the most common malignancy in women and a public health problem worldwide. Breast cancer is often accompanied by an inflammatory process characterized by the presence of proinflammatory cytokines such as tumor necrosis factor (TNF-α), which has important implications in the course of the disease. Inflammation has been described primarily as a favorable environment for tumor development. However, under certain conditions TNF-α can promote signals for activation, differentiation, survival or cell death, so the study of the variants of this cytokine, its receptors, the presence of polymorphisms and its implication in different phenotypes of breast cancer is necessary...
December 4, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29183282/bilateral-muscle-fiber-and-nerve-influences-by-tnf-alpha-in-response-to-unilateral-muscle-overuse-studies-on-tnf-receptor-expressions
#10
Lina Renström, Per Stål, Yafeng Song, Sture Forsgren
BACKGROUND: TNF-alpha is suggested to be involved in muscle damage and muscle inflammation (myositis). In order to evaluate whether TNF-alpha is involved in the myositis that occurs in response to muscle overuse, the aim was to examine the expression patterns of TNF receptors in this condition. METHODS: A rabbit muscle overuse model leading to myositis in the soleus muscle was used. The expression patterns of the two TNF receptors Tumor Necrosis Factor Receptor type 1 (TNFR1) and Tumor Necrosis Factor Receptor type 2 (TNFR2) were investigated...
November 28, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29176974/inhibition-of-epithelial-tnf-%C3%AE-receptors-by-purified-fruit-bromelain-ameliorates-intestinal-inflammation-and-barrier-dysfunction-in-colitis
#11
Zijuan Zhou, Liang Wang, Panpan Feng, Lianhong Yin, Chen Wang, Shengxu Zhi, Jianyi Dong, Jingyu Wang, Yuan Lin, Dapeng Chen, Yongjian Xiong, Jinyong Peng
Activation of the TNF-α receptor (TNFR) leads to an inflammatory response, and anti-TNF therapy has been administered to reduce inflammation symptoms and heal mucosal ulcers in inflammatory bowel disease (IBD). Bromelain, a complex natural mixture of proteolytic enzymes, has been shown to exert anti-inflammatory effects. This study aimed to investigate the effect of purified fruit bromelain (PFB)-induced inhibition of epithelial TNFR in a rat colitis model. Colitis was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163543/interleukin-6-present-in-inflammatory-ascites-from-advanced-epithelial-ovarian-cancer-patients-promotes-tumor-necrosis-factor-receptor-2-expressing-regulatory-t-cells
#12
Nirmala Chandralega Kampan, Mutsa Tatenda Madondo, Orla M McNally, Andrew N Stephens, Michael A Quinn, Magdalena Plebanski
Background: Epithelial ovarian cancer (EOC) remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs) in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2), as well as pro-inflammatory factors such as interleukin 6 (IL-6) and tumor necrosis factor (TNF)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163535/chronic-inflammation-increases-the-sensitivity-of-mouse-treg-for-tnfr2-costimulation
#13
Tobias Schmid, Lena Falter, Sabine Weber, Nils Müller, Konstantin Molitor, David Zeller, Dorothea Weber-Steffens, Thomas Hehlgans, Harald Wajant, Sven Mostböck, Daniela N Männel
TNF receptor type 2 (TNFR2) has gained attention as a costimulatory receptor for T cells and as critical factor for the development of regulatory T cells (Treg) and myeloid suppressor cells. Using the TNFR2-specific agonist TNCscTNF80, direct effects of TNFR2 activation on myeloid cells and T cells were investigated in mice. In vitro, TNCscTNF80 induced T cell proliferation in a costimulatory fashion, and also supported in vitro expansion of Treg cells. In addition, activation of TNFR2 retarded differentiation of bone marrow-derived immature myeloid cells in culture and reduced their suppressor function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158612/detection-of-pathological-changes-in-the-aorta-during-thoracic-aortic-aneurysm-progression-on-molecular-level
#14
Miroslava Rabajdová, Peter Urban, Ivana Špaková, Artemiou Panagiotis, Michaela Ferenčáková, Dušan Rybár, Nikita Bobrov, František Sabol, Mária Mareková
The progression of thoracic aortic aneurysm depends on regulation of aortic wall homeostasis and on changes in the structural components of the extracellular matrix, which are affected by multiple molecular signalling pathways. We decided to correlate the diameter of ascending thoracic aneurysm with gene expression of inflammation markers (IL-6, CRP), cytokine receptors (IL-6R, TNFR1, and TNFR2), and extracellular matrix components (Emilin-1, MMP9, and TIMP) for detection of the degree of pathological process of TAA formation...
2017: Disease Markers
https://www.readbyqxmd.com/read/29155425/granulocyte-derived-tnf%C3%AE-promotes-vascular-and-hematopoietic-regeneration-in-the-bone-marrow
#15
Emily Bowers, Anastasiya Slaughter, Paul S Frenette, Rork Kuick, Oscar M Pello, Daniel Lucas
Endothelial cells are a critical component of the bone marrow (BM) stromal network, which maintains and regulates hematopoietic cells. Vascular regeneration precedes, and is necessary for, successful hematopoietic stem cell (HSC) transplantation, the only cure for most hematopoietic diseases. Recent data suggest that mature hematopoietic cells regulate BM stromal-cell function. Whether a similar cross-talk regulates the BM vasculature is not known. Here we found that donor hematopoietic cells act on sinusoidal endothelial cells and induce host blood vessel and hematopoietic regeneration after BM transplantation in mice...
November 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29113822/lack-of-tnf-%C3%AE-signaling-through-p55-makes-the-mice-more-susceptible-to-acute-infection-but-does-not-alter-state-of-latency-and-reactivation-of-hsv-1
#16
Aditi Mohankrishnan, Rajesh Parmar, Vishakha Bhurani, Sarat Kumar Dalai
TNF-α has been shown to play an important role in pathogenesis and latency of HSV-1 infections. TNF-α signals through TNFR1 (p55) and TNFR2 (p75), and signaling through p55 generally results in gene activation leading to induction of inflammatory responses. Here, we studied the role of TNF-α signaling in latent virus reactivation in p55-knock out (KO) mouse model of ocular HSV-1 infection. We found that KO mice are more susceptible to HSV-1 infection compared to wild type C57Bl/6 mice. While the absence of TNFRI signaling enhanced the ganglion latent DNA content by two folds, there was no difference in the maintenance and reactivation of latent HSV-1...
November 4, 2017: Virus Research
https://www.readbyqxmd.com/read/29081600/amyotrophic-lateral-sclerosis-a-multisystem-pathology-insights-into-the-role-of-tnf%C3%AE
#17
REVIEW
Massimo Tortarolo, Daniele Lo Coco, Pietro Veglianese, Antonio Vallarola, Maria Teresa Giordana, Gabriella Marcon, Ettore Beghi, Marco Poloni, Michael J Strong, Anand M Iyer, Eleonora Aronica, Caterina Bendotti
Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFα is one of the major players governing the inflammation in the central nervous system and peripheral districts such as the neuromuscular and immune system. Changes in TNFα levels are reported in blood, cerebrospinal fluid, and nerve tissues of ALS patients and animal models. However, whether they play a detrimental or protective role on the disease progression is still not clear...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29080421/molecular-mechanism-of-gd-c82-oh-22-increasing-collagen-expression-implication-for-encaging-tumor
#18
Jing Liu, Seung-Gu Kang, Peng Wang, Yue Wang, Xiaonan Lv, Ying Liu, Fei Wang, Zonglin Gu, Zaixing Yang, Jeffrey K Weber, Ning Tao, Zhihai Qin, Qing Miao, Chunying Chen, Ruhong Zhou, Yuliang Zhao
Gadolinium-containing fullerenol Gd@C82(OH)22 has demonstrated low-toxicity and highly therapeutic efficacy in inhibiting tumor growth and metastasis through new strategy of encaging cancer, however, little is known about the mechanisms how this nanoparticle regulates fibroblast cells to prison (instead of poison) cancer cells. Here, we report that Gd@C82(OH)22 promote the binding activity of tumor necrosis factor (TNFα) to tumor necrosis factor receptors 2 (TNFR2), activate TNFR2/p38 MAPK signaling pathway to increase cellular collagen expression in fibrosarcoma cells and human primary lung cancer associated fibroblasts isolated from patients...
October 16, 2017: Biomaterials
https://www.readbyqxmd.com/read/29062765/genes-of-tumor-necrosis-factors-and-their-receptors-and-the-primary-open-angle-glaucoma-in-the-population-of-central-russia
#19
Evgeniya Tikunova, Veronika Ovtcharova, Evgeny Reshetnikov, Volodymyr Dvornyk, Alexey Polonikov, Olga Bushueva, Mikhail Churnosov
AIM: To examine the association of genetic polymorphisms (-308)G/A TNFα, (+250)A/G Ltα, (+36)A/G TNFR1, (+1663)A/G TNFR2 with the development of primary open angle glaucoma (POAG) among people in Central Russia. METHODS: The study sample included 443 individuals, of which 252 patients with POAG and 191 individuals in the control group. Genotyping of (-308)G/A TNFα, (+250)A/G Ltα, (+36)A/G TNFR1, (+1663)A/G TNFR2 was performed using polymerase chain reaction...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29057962/tnfr1-inhibition-with-a-nanobody-protects-against-eae-development-in-mice
#20
Sophie Steeland, Sara Van Ryckeghem, Griet Van Imschoot, Riet De Rycke, Wendy Toussaint, Leen Vanhoutte, Christian Vanhove, Filip De Vos, Roosmarijn E Vandenbroucke, Claude Libert
TNF has as detrimental role in multiple sclerosis (MS), however, anti-TNF medication is not working. Selective TNF/TNFR1 inhibition whilst sparing TNFR2 signaling reduces the pro-inflammatory effects of TNF but preserves the important neuroprotective signals via TNFR2. We previously reported the generation of a Nanobody-based selective inhibitor of human TNFR1, TROS that will be tested in experimental autoimmune encephalomyelitis (EAE). We specifically antagonized TNF/TNFR1 signaling using TROS in a murine model of MS, namely MOG35-55-induced EAE...
October 20, 2017: Scientific Reports
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