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https://www.readbyqxmd.com/read/27898403/role-of-osteoprotegerin-opg-in-bone-marrow-adipogenesis
#1
Lili Zhang, Mengmeng Liu, Xiaokang Zhou, Yi Liu, Bo Jing, Xiaogang Wang, Qi Zhang, Yao Sun
BACKGROUND/AIMS: Bone marrow adipogenesis is one of the major characteristics of aged bone. Bone marrow mesenchymal stem cells (BMMSCs) prefer to differentiate into adipocytes instead of osteoblasts in the bone marrow cavity in aged hosts. The mechanism of formation and function of adipocytes in aged bone marrow needs further investigation. Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor (TNFR) super family, and it can inhibit the activities of osteoclasts. We found that adipocyte numbers increased in the bone marrow of Opg knockout mice...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27895978/cytokines-and-cytokine-receptors-involved-in-the-pathogenesis-of-alzheimer-s-disease
#2
Tomone Nagae, Kiho Araki, Yuki Shimoda, Lucia I Sue, Thomas G Beach, Yoshihiro Konishi
Inflammatory mechanisms are implicated in the pathology of Alzheimer's disease (AD). However, it is unclear whether inflammatory alterations are a cause or consequence of neurodegeneration leading to dementia. Clarifying this issue would provide valuable insight into the early diagnosis and therapeutic management of AD. To address this, we compared the mRNA expression profiles of cytokines in the brains of AD patients with "non-demented individuals with AD pathology" and non-demented healthy control (ND) individuals...
August 2016: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/27872207/myeloid-specific-gene-deletion-of-protein-phosphatase-2a-magnifies-myd88-and-trif-dependent-inflammation-following-endotoxin-challenge
#3
Lei Sun, Tiffany T Pham, Timothy T Cornell, Kelli L McDonough, Walker M McHugh, Neal B Blatt, Mary K Dahmer, Thomas P Shanley
Protein phosphatase 2A (PP2A) is a member of the intracellular serine/threonine phosphatases. Innate immune cell activation triggered by pathogen-associated molecular patterns is mediated by various protein kinases, and PP2A plays a counter-regulatory role by deactivating these kinases. In this study, we generated a conditional knockout of the α isoform of the catalytic subunit of PP2A (PP2ACα). After crossing with myeloid-specific cre-expressing mice, effective gene knockout was achieved in various myeloid cells...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27869172/a-redox-state-dictated-signalling-pathway-deciphers-the-malignant-cell-specificity-of-cd40-mediated-apoptosis
#4
C J Dunnill, K Ibraheem, A Mohamed, J Southgate, N T Georgopoulos
CD40, a member of the tumour necrosis factor receptor (TNFR) superfamily, has the capacity to cause extensive apoptosis in carcinoma cells, while sparing normal epithelial cells. Yet, apoptosis is only achieved by membrane-presented CD40 ligand (mCD40L), as soluble receptor agonists are but weakly pro-apoptotic. Here, for the first time we have identified the precise signalling cascade underpinning mCD40L-mediated death as involving sequential TRAF3 stabilisation, ASK1 phosphorylation, MKK4 (but not MKK7) activation and JNK/AP-1 induction, leading to a Bak- and Bax-dependent mitochondrial apoptosis pathway...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27863204/tnf-and-il-18-cytokines-may-regulate-liver-fat-storage-under-homeostasis-conditions
#5
Jaqueline Pereira Lana, Laís Bhering Martins, Marina Chaves de Oliveira, Zélia Menezes-Garcia, Letícia Tamie Pavia Yamada, Leda Quercia Vieira, Mauro Martins Teixeira, Adaliene Versiani Matos Ferreira
The inflammation induced by obesogenic diets is associated with deposition of fat in the liver. On the other hand, anti-inflammatory and immunosuppressive therapies may impact in body fat storage and in liver lipid dynamics. It is important to study specific inflammatory mediators in this context, since their role on hepatic damage is not fully clarified. This study aimed to evaluate the role of interleukin (IL)-18 and tumor necrosis factor (TNF) receptor in liver dysfunction induced by diet. Male C57BL/6 wild-type (WT), IL-18, and TNF receptor 1 knockout mice (IL-18(-/-) and TNFR1(-/-)) were divided according to the experimental diets: chow diet or a high-refined carbohydrate-containing diet...
December 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
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
#6
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/27856634/fc-engineering-approaches-to-enhance-the-agonism-and-effector-functions-of-an-anti-ox40-antibody
#7
Di Zhang, Monica V Goldberg, Mark L Chiu
Agonistic antibodies directed against immunostimulatory receptors belonging to the tumor necrosis factor receptor (TNFR) superfamily are emerging as promising cancer immunotherapies. Several Fc engineering approaches were discovered recently that can augment the anti-tumor activities of TNFR antibodies by enhancing their agonistic activities and/or effector functions. In this study, we evaluated and compared these approaches for their effects on an anti-OX40 antibody. Both S267E/L328F and V12 mutations of an anti-OX40 antibody can facilitate enhanced binding to FcγRIIB and result in increased FcγRIIB crosslinking mediated agonist activity...
November 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27832933/a-plant-cell-expressed-recombinant-anti-tnf-fusion-protein-is-biologically-active-in-the-gut-and-alleviates-immune-mediated-hepatitis-and-colitis
#8
Yaron Ilan, Svetlana Gingis-Velitski, Ami Ben Ya'aco, Yehudit Shabbat, Lidya Zolotarov, Einat Almon, Yoseph Shaaltiel
: The orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) (n=6) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human antibody IgG1 domain. AIM: To evaluate the immune modulatory effect of the oral administration of plant cells expressing PRX-106. METHODS: Mice treated with Concanavalin A (ConA) to induce immune hepatitis was orally treated with cells expressing PRX-106 containing 0...
November 4, 2016: Immunobiology
https://www.readbyqxmd.com/read/27814644/the-nf-kb-regulates-the-shp-1-expression-in-monocytes-in-congestive-heart-failure
#9
Mirko Pesce, Sara Franceschelli, Alessio Ferrone, Antonia Patruno, Alfredo Grilli, Maria Anna De Lutiis, Francesca R Pluchinotta, Sonia Bergante, Guido Tettamanti, Graziano Riccioni, Mario Felaco, Lorenza Speranza
It has been shown that functional recovery of patients with acute congestive heart failure (ACHF) after treatment with conventional drugs (CD) is mediated by suppression of inflammation in peripheral blood mononuclear cells. Here, we analyzed gene expression profiles of monocytes from symptomatic ACHF patients (NYHA Class III-IV) before and after pharmacological treatment with CD. The treatment was associated with selective down-regulation of "TNFR signaling" and pro-inflammatory mediators CCL5, MIP-1α receptor, CD14, ITGAM, and significant up-regulation of "TNFR signaling" as evidenced by increase in anti-inflammatory factors including NF-kBIA, TNFAIP3 and SHP-1...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27796312/ubc13-haploinsufficiency-protects-against-age-related-insulin-resistance-and-high-fat-diet-induced-obesity
#10
Erina Joo, Toru Fukushima, Norio Harada, John C Reed, Shu-Ichi Matsuzawa, Nobuya Inagaki
Obesity is associated with low-grade inflammation that leads to insulin resistance and type 2 diabetes via Toll-like Receptor (TLR) and TNF-family cytokine receptor (TNFR) signaling pathways. Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical K63-linked polyubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in TLR and TNFR pathways. However, the relationship between Ubc13 and metabolic disease remains unclear. In this study, we investigated the role of Ubc13 in insulin resistance and high-fat diet (HFD)-induced obesity...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27791020/essential-protective-role-of-tumor-necrosis-factor-receptor-2-in-neurodegeneration
#11
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/27764793/dcr3-induces-epithelial-mesenchymal-transition-through-activation-of-the-tgf-%C3%AE-3-smad-signaling-pathway-in-crc
#12
Yan-Ping Liu, Hui-Fang Zhu, Ding-Li Liu, Zhi-Yan Hu, Sheng-Nan Li, He-Ping Kan, Xiao-Yan Wang, Zu-Guo Li
Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo...
October 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27734112/anti-gitr-therapy-promotes-immunity-against-malignant-glioma-in-a-murine-model
#13
Jason Miska, Aida Rashidi, Alan L Chang, Megan E Muroski, Yu Han, Lingjiao Zhang, Maciej S Lesniak
Regulatory T cells (Tregs) are potently immunosuppressive cells that accumulate within the glioma microenvironment. The reduction in their function and/or trafficking has been previously shown to enhance survival in preclinical models of glioma. Glucocorticoid-induced TNFR-related protein (GITR) is a tumor necrosis factor superfamily receptor enriched on Tregs that has shown promise as a target for immunotherapy. An agonistic antibody against GITR has been demonstrated to inhibit Tregs in a number of models and has only been recently addressed in glioma...
December 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27733552/cell-extrinsic-tnf-collaborates-with-trif-signaling-to-promote-yersinia-induced-apoptosis
#14
Lance W Peterson, Naomi H Philip, Christopher P Dillon, John Bertin, Peter J Gough, Douglas R Green, Igor E Brodsky
Innate immune responses that are crucial for control of infection are often targeted by microbial pathogens. Blockade of NF-κB and MAPK signaling by the Yersinia virulence factor YopJ inhibits cytokine production by innate immune cells but also triggers cell death. This cell death requires RIPK1 kinase activity and caspase-8, which are engaged by TLR4 and the adaptor protein TRIF. Nevertheless, TLR4- and TRIF-deficient cells undergo significant apoptosis, implicating TLR4/TRIF-independent pathways in the death of Yersinia-infected cells...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27681126/suppression-of-host-innate-immune-response-by-hepatitis-c-virus-via-induction-of-autophagic-degradation-of-traf6
#15
Stephanie T Chan, Jiyoung Lee, Mansi Narula, J-H James Ou
: Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an important adaptor molecule that mediates the TNFR family and interleukin-1 (IL-1)/Toll-like receptor (TLR) signaling cascades. These pathways are important for the host to control viral infections. In this report, we demonstrated that hepatitis C virus (HCV) depleted TRAF6 from its host cells through a posttranslational mechanism. This depletion was independent of proteasomes, as it was not affected by the proteasome inhibitor MG132, but it was suppressed by bafilomycin A1, which led to the association of TRAF6 with autophagosomes...
December 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27670158/cd16-is-indispensable-for-antibody-dependent-cellular-cytotoxicity-by-human-monocytes
#16
Wei Hseun Yeap, Kok Loon Wong, Noriko Shimasaki, Esmeralda Chi Yuan Teo, Jeffrey Kim Siang Quek, Hao Xiang Yong, Colin Phipps Diong, Antonio Bertoletti, Yeh Ching Linn, Siew Cheng Wong
Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16- expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27640805/association-of-tnfrsf1b-676-gene-polymorphism-with-the-risk-of-rheumatoid-arthritis-in-han-chinese-population-in-hunan
#17
Xi Xie, Fen Li, Jinwei Chen, Jiesheng Gao, Fanggen Lu
OBJECTIVE: To study the association of TNFRSF1B +676 gene (rs1061622) polymorphism with the risk of rheumatoid arthritis (RA ) in Han Chinese population of Hunan. METHODS: A total of 112 patients with RA from Han Chinese population in Hunan were recruited, along with 129 healthy controls. TNFRSF1B +676 (rs1061622) gene polymorphisms were examined by PCR-RFLP. Serum levels of soluble TNFR II were analyzed by ELISA. RESULTS: RA patients displayed a similar TNFRSF1B +676 genotype to controls (GG/TG/TT: 5/62/45 vs 9/56/64, P=0...
September 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/27639807/rectal-delivery-of-a-dnazyme-that-specifically-blocks-the-transcription-factor-gata3-and-reduces-colitis-in-mice
#18
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/27635695/spata2-new-insights-in-the-assembly-of-the-tnfr-signaling-complex
#19
Lisa Schlicher, Ulrich Maurer
No abstract text is available yet for this article.
September 16, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27629532/possible-mechanisms-of-leukoagglutinin-induced-apoptosis-in-human-cells-in-vitro
#20
Tetiana Kochubei, Volodymyr Kitam, Oksana Maksymchuk, Oksana Piven, Lyubov Lukash
Leukoagglutinin is one of the phytohemagglutinin isolectins isolated from Phaseolus vulgaris. In our recent study, we showed that this lectin is able to influence the growth of human cancer cells in vitro. In addition, using the acridine orange and ethidium bromide staining, we found that leukoagglutinin can induce apoptosis. In order to understand the molecular mechanisms of induction of apoptosis, we performed computational modeling with subsequent experimental verification of theoretical data in vitro. We developed computational models of leukoagglutinin interaction with pro- (FasR and TNFR) and anti-apoptotic (IGF-1 and EGFR) receptors, and confirmed that leukoagglutinin may specifically interact with these receptors...
September 15, 2016: Cell Biology International
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