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https://www.readbyqxmd.com/read/28092866/transmembrane-tumor-necrosis-factor-%C3%AE-promotes-the-recruitment-of-mdscs-to-tumor-tissue-by-upregulating-cxcr4-expression-via-tnfr2
#1
Hongping Ba, Baihua Li, Xiaoyan Li, Cheng Li, Anlin Feng, Yazhen Zhu, Jing Wang, Zhuoya Li, Bingjiao Yin
Myeloid-derived suppressor cells (MDSCs) accumulated in tumor sites promote immune evasion. We found that TNFR deficiency-induced rejection of transplanted tumor was accompanied with markedly decreased accumulation of MDSCs. However, the mechanism(s) behind this phenomenon is not completely understood. Here, we demonstrated that TNFR deficiency did not affect the amount of MDSCs in bone marrow (BM), but decreased accumulation of Gr-1(+)CD11b(+) MDSCs in the spleen and tumor tissues. The chemotaxis of Tnfr(-/-) MDSCs was prominently decreased in response to both tumor cell culture supernatants and tumor tissue homogenates from Tnfr(-/-) and wild-type mice, indicating an effect of TNFR signaling on chemokine receptor expression in MDSCs...
January 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28087739/tnf-signaling-through-rip1-kinase-enhances-sn38-induced-death-in-colon-adenocarcinoma
#2
Lucia Cabal-Hierro, Peter J O'Dwyer
: Elucidation of tumor necrosis factor (TNF)-directed mechanisms for cell death induction and maintenance of tumor growth has revealed a role for receptor-interacting protein kinases 1 and 3 (RIPK1/RIP1 and RIPK3/RIP3), components of the necrosome complex, as determinants of cell fate. Here the participation of TNF signaling was analyzed with regard to the cytotoxic action of different DNA damaging agents in a panel of colon cancer cells. While most of these cell lines were insensitive to TNF, combination with these drugs increased sensitivity by inducing cell death and DNA damage, especially in the case of the topoisomerase inhibitor SN38...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28066794/altered-monocyte-and-endothelial-cell-adhesion-molecule-expression-is-linked-to-vascular-inflammation-in-human-immunodeficiency-virus-infection
#3
Manjusha Kulkarni, Emily Bowman, Janelle Gabriel, Taylor Amburgy, Elizabeth Mayne, David A Zidar, Courtney Maierhofer, Abigail Norris Turner, Jose A Bazan, Susan L Koletar, Michael M Lederman, Scott F Sieg, Nicholas T Funderburg
BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium. METHODS: Monocyte subsets (CD14(+)CD16(-), CD14(+)CD16(+), CD14(Dim)CD16(+)) from HIV negative (HIV(-)) and antiretroviral therapy-treated HIV positive (HIV(+)) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28013046/loss-of-tradd-attenuates-pressure-overload-induced-cardiac-hypertrophy-through-regulating-tak1-p38-mapk-signalling-in-mice
#4
Lianpin Wu, Zhiyong Cao, Liqin Mei, Ling Ji, Qike Jin, Jingjing Zeng, Jiafeng Lin, Maoping Chu, Lei Li, Xiangjun Yang
We investigated the role of tumour necrosis factor receptor (TNFR)-associated death domain (TRADD) on pressure overload-induced cardiac hypertrophy and the underlying molecular mechanisms by using a TRADD deficiency mice model. 6-8 weeks wild-type and TRADD knockout mice were performed to transverse aorta constriction (TAC) or sham operation (6-8 mice for each group). 14 days after TAC, cardiac function was measured by echocardiography, as well as by pathological and molecular analyses of heart samples. The expressions of cardiac hypertrophic and fibrotic markers were detected by qPCR...
December 21, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27979472/regulation-of-myocardial-stromal-cell-derived-factor-1%C3%AE-cxcl12-by-tumor-necrosis-factor-signaling
#5
Meijing Wang, Lina Wang, Chunyan Huang, I-Wen Wang, Mark W Turrentine
BACKGROUND: Global myocardial ischemia-reperfusion (I/R) occurs during cardiac operations. This I/R injury leads to increased production of tumor necrosis factor α (TNF) instantly and upregulated expression of stromal cell-derived factor 1 α (SDF-1). On the basis of the published data from our laboratory and other groups, locally produced TNF contributes to cardiac dysfunction mainly via binding to its receptor (tumor necrosis factor receptor 1 [TNFR1]), whereas ischemia-induced myocardial SDF-1 mediates cardioprotection...
January 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/27939488/first-and-second-trimester-immune-biomarkers-in-preeclamptic-and-normotensive-women
#6
Brandie D Taylor, Roberta B Ness, Mark A Klebanoff, Roger Zoh, Debra Bass, David M Hougaard, Kristin Skogstrand, Catherine L Haggerty
INTRODUCTION: Circulating immune markers may be associated with preeclampsia but further investigations in early pregnancy and among preeclampsia subtypes are warranted. We examined immune markers in 208 preeclamptic women and 411 normotensive controls. METHODS: Our study was nested within the Collaborative Perinatal Project. A total of 242 women had first trimester serum samples and 392 had second trimester serum samples. Preeclampsia was defined as hypertension >20weeks of gestation with proteinuria or pulmonary edema, oliguria, or convulsions...
October 2016: Pregnancy Hypertension
https://www.readbyqxmd.com/read/27898403/role-of-osteoprotegerin-opg-in-bone-marrow-adipogenesis
#7
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...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27895978/cytokines-and-cytokine-receptors-involved-in-the-pathogenesis-of-alzheimer-s-disease
#8
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
#9
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...
January 1, 2017: 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
#10
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
#11
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
#12
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
#13
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 discovered recently can augment the anti-tumor activities of TNFR antibodies by enhancing their agonistic activities and/or effector functions. In this study, we compared these approaches for their effects on an anti-OX40 antibody. Both S267E/L328F and V12 mutations facilitated enhanced binding to FcγRIIB and thus increased FcγRIIB cross-linking mediated agonist activity...
December 30, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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