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https://www.readbyqxmd.com/read/27911915/marathon-race-affects-neutrophil-surface-molecules-role-of-inflammatory-mediators
#1
Vinicius Coneglian Santos, Ana Paula Renno Sierra, Rodrigo Oliveira, Kim Guimarães Caçula, César Miguel Momesso, Fabio Takeo Sato, Maysa Braga Barros Silva, Heloisa Helena Oliveira, Maria Elizabeth Pereira Passos, Diego Ribeiro de Souza, Olivia Santos Gondim, Marino Benetti, Adriana Cristina Levada-Pires, Nabil Ghorayeb, Maria Augusta Peduti Dal Molin Kiss, Renata Gorjão, Tânia Cristina Pithon-Curi, Maria Fernanda Cury-Boaventura
The fatigue induced by marathon races was observed in terms of inflammatory and immunological outcomes. Neutrophil survival and activation are essential for inflammation resolution and contributes directly to the pathogenesis of many infectious and inflammatory conditions. The aim of this study was to investigate the effect of marathon races on surface molecules related to neutrophil adhesion and extrinsic apoptosis pathway and its association with inflammatory markers. We evaluated 23 trained male runners at the São Paulo International Marathon 2013...
2016: PloS One
https://www.readbyqxmd.com/read/27899821/activation-of-tnfr2-sensitizes-macrophages-for-tnfr1-mediated-necroptosis
#2
Daniela Siegmund, Juliane Kums, Martin Ehrenschwender, Harald Wajant
Macrophages express TNFR1 as well as TNFR2 and are also major producers of tumor necrosis factor (TNF), especially upon contact with pathogen-associated molecular patterns. Consequently, TNF not only acts as a macrophage-derived effector molecule but also regulates the activity and viability of macrophages. Here, we investigated the individual contribution of TNFR1 and TNFR2 to TNF-induced cell death in macrophages. Exclusive stimulation of TNFR1 showed no cytotoxic effect whereas selective stimulation of TNFR2 displayed mild cytotoxicity...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27895032/molecular-pathways-receptor-ectodomain-shedding-in-treatment-resistance-and-monitoring-of-cancer
#3
Miles A Miller, Ryan J Sullivan, Douglas A Lauffenburger
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK)...
November 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27889231/nimbolide-inhibits-androgen-independent-prostate-cancer-cells-survival-and-proliferation-by-modulating-multiple-pro-survival-signaling-pathways
#4
P Raja Singh, E Sugantha Priya, S Balakrishnan, R Arunkumar, G Sharmila, M Rajalakshmi, J Arunakaran
BACKGROUND: Prostate cancer is the most prominent cancer in men, experiencing a relapse in disease often express high serum TNF-α levels. It has been correlated with increased cell survival and proliferation of prostate cancer cells. Previous studies reported that nimbolide, a terpenoid derived from the leaves and flowers of neem tree inhibits cancer growth through selective modulation of cell signaling pathways linked to inflammation, survival, proliferation, angiogenesis and metastasis...
November 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27879679/hydrostatin-tl1-an-anti-inflammatory-active-peptide-from-the-venom-gland-of-hydrophis-cyanocinctus-in-the-south-china-sea
#5
Ningyuan Wang, Yan Huang, An Li, Hailong Jiang, Jie Wang, Jianzhong Li, Lei Qiu, Ka Li, Yiming Lu
Tumor necrosis factor (TNF)-α is a pleiotropic cytokine with intense pro-inflammatory and immunomodulatory properties, and anti-TNF-α biologics are effective therapies for various inflammatory diseases such as inflammatory bowel disease (IBD) and sepsis. Snake venom, as a traditional Chinese medicine, has been used in the treatment of inflammatory diseases in China for centuries. In this research, we constructed a venom gland T7 phage display library of the sea snake Hydrophis cyanocinctus to screen bioactive compounds that antagonize TNF-α and identified a novel nine-amino-acid peptide, termed hydrostatin-TL1 (H-TL1)...
November 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27869161/therapeutic-targeting-of-necroptosis-by-smac-mimetic-bypasses-apoptosis-resistance-in-acute-myeloid-leukemia-cells
#6
C Safferthal, K Rohde, S Fulda
Resistance to apoptosis, for example due to overexpression of Inhibitor of Apoptosis (IAP) proteins, is associated with poor prognosis in acute myeloid leukemia (AML). Here, we identify that Smac mimetics such as BV6, which antagonizes IAP proteins, elicit necroptosis in AML cells, in which apoptosis is inhibited pharmacologically by caspase inhibitors or genetically by caspase-8 knockdown. Importantly, BV6 triggers necroptosis also in apoptosis-resistant patient-derived AML blasts, underlining the clinical relevance of our findings...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27864283/tumor-necrosis-factor-%C3%AE-a-key-contributor-to-intervertebral-disc-degeneration
#7
REVIEW
Cheng Wang, Xiaohua Yu, Yiguo Yan, Wei Yang, Shujun Zhang, Yongxiao Xiang, Jian Zhang, Wenjun Wang
Intervertebral disc (IVD) degeneration (IDD) is the most common cause leading to low back pain (LBP), which is a highly prevalent, costly, and crippling condition worldwide. Current treatments for IDD are limited to treat the symptoms and do not target the pathophysiology. Tumor necrosis factor-α (TNF-α) is one of the most potent pro-inflammatory cytokines and signals through its receptors TNFR1 and TNFR2. TNF-α is highly expressed in degenerative IVD tissues, and it is deeply involved in multiple pathological processes of disc degeneration, including matrix destruction, inflammatory responses, apoptosis, autophagy, and cell proliferation...
November 17, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27863204/tnf-and-il-18-cytokines-may-regulate-liver-fat-storage-under-homeostasis-conditions
#8
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/27834853/brefeldin-a-inhibited-guanine-nucleotide-exchange-factor-1-big1-governs-the-recruitment-of-tumor-necrosis-factor-receptor-associated-factor-2-traf2-to-tumor-necrosis-factor-receptor-1-tnfr1-signaling-complexes
#9
Takuya Noguchi, Mei Tsuchida, Yosuke Kogue, Christian Spadini, Yusuke Hirata, Atsushi Matsuzawa
Tumor necrosis factor receptor-associated factor 2 (TRAF2) is a critical mediator of tumor necrosis factor-α (TNF-α) signaling. However, the regulatory mechanisms of TRAF2 are not fully understood. Here we show evidence that TRAF2 requires brefeldin A-inhibited guanine nucleotide-exchange factor 1 (BIG1) to be recruited into TNF receptor 1 (TNFR1) signaling complexes. In BIG1 knockdown cells, TNF-α-induced c-Jun N-terminal kinase (JNK) activation was attenuated and the sensitivity to TNF-α-induced apoptosis was increased...
November 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27834133/the-effects-of-colchicum-baytopiorum-on-regulatory-genes-of-apoptotic-and-autophagic-cell-death-in-hela-cells
#10
Özlem D Özsöylemez, Melek Öztürk, Nurhayat Sütlüpinar, Sera Kayacan, Matem Tunçdemir, Gül Özcan
BACKGROUND: The natural products have increasing important for the development of anticancer agents. Colchicum baytopiorum C.D.Brickell (C. baytopiorum), an endemic species for Turkey, contains colchicine and its derivatives. Stimulation of apoptotic and autophagy-mediated cell deaths are effective strategy for anticancer therapies. AIM: The aim of the study is to determine the role of the extract on both apoptotic and autophagic cell death in HeLa cell line. METHODS: The cell viability of C...
November 9, 2016: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/27832801/gene-expression-comparison-reveals-distinct-basal-expression-of-hox-members-and-differential-tnf-induced-response-between-brain-and-spinal-cord-derived-microvascular-endothelial-cells
#11
Yves Molino, Françoise Jabès, Amandine Bonnet, Nicolas Gaudin, Anne Bernard, Philippe Benech, Michel Khrestchatisky
BACKGROUND: The heterogeneity of endothelial cell types underlies their remarkable ability to sub-specialize and provide specific requirements for a given vascular bed. Here, we compared rat microvascular endothelial cells (MECs) derived from the brain and spinal cord in both basal and inflammatory conditions. METHODS: We used whole rat genome microarrays to compare, at different time points, basal and TNF-α-induced gene expression of rat MECs from in vitro models of the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB)...
November 10, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27811014/regulated-necrosis-related-molecule-mrna-expression-in-humans-mice-and-murine-acute-tissue-injury-systemic-autoimmunity-leading-to-progressive-organ-damage-and-progressive-fibrosis
#12
Mohsen Honarpisheh, Jyaysi Desai, Julian A Marschner, Marc Weidenbusch, Maciej Lech, Volker Vielhauer, Hans-Joachim Anders, Shrikant R Mulay
The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of TNFR1, RIPK1, RIPK3, MLKL, CASP8, FADD, CIAP1, CIAP2, GPX4, CYPD, CASP1, NLRP3, and PARP1 in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice. In addition, we characterized their expression profiles in acute as well as persistent tissue injury and chronic tissue remodeling using acute and chronic kidney injury models...
November 3, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27806130/mycobacterium-abscessus-induced-granuloma-formation-is-strictly-dependent-on-tnf-signaling-and-neutrophil-trafficking
#13
Audrey Bernut, Mai Nguyen-Chi, Iman Halloum, Jean-Louis Herrmann, Georges Lutfalla, Laurent Kremer
Mycobacterium abscessus is considered the most common respiratory pathogen among the rapidly growing non-tuberculous mycobacteria. Infections with M. abscessus are increasingly found in patients with chronic lung diseases, especially cystic fibrosis, and are often refractory to antibiotic therapy. M. abscessus has two morphotypes with distinct effects on host cells and biological responses. The smooth (S) variant is recognized as the initial airway colonizer while the rough (R) is known to be a potent inflammatory inducer associated with invasive disease, but the underlying immunopathological mechanisms of the infection remain unsolved...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27791020/essential-protective-role-of-tumor-necrosis-factor-receptor-2-in-neurodegeneration
#14
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/27777599/frailty-has-a-stronger-association-with-inflammation-than-age-in-older-veterans
#15
P Van Epps, D Oswald, P A Higgins, T R Hornick, H Aung, R E Banks, B M Wilson, C Burant, S Graventstein, D H Canaday
BACKGROUND: Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans. RESULTS: We analyzed 117 subjects (age range 62-95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty...
2016: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/27755992/a-new-form-of-amphotericin-b-the-complex-with-copper-ii-ions-downregulates-stnfr1-shedding-and-changes-the-activity-of-genes-involved-in-tnf-induced-pathways-amb-cu-2-downregulates-stnfr1-shedding-and-changes-the-activity-of-genes-involved-in-tnf-induced-pathways
#16
Joanna Gola, Barbara Strzałka-Mrozik, Celina Kruszniewska-Rajs, Adrian Janiszewski, Bartłomiej Skowronek, Mariusz Gagoś, Grzegorz Czernel, Urszula Mazurek
BACKGROUND: A new form of amphotericin B (AmB)- complex with copper (II) ions (AmB-Cu(2+)) - is less toxic to human renal cells. Cytokines, including Tumor Necrosis Factor (TNF), are responsible for nephrotoxicity observed in patients treated with AmB. Another problem during therapy is the occurrence of oxidized forms of AmB (AmB-ox) in patients' circulation. To elucidate the molecular mechanism responsible for the reduction of the toxicity of AmB-Cu(2+), we evaluated the expression of genes encoding TNF and its receptors alongside encoding proteins involved in TNF-induced signalization...
September 5, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27755542/selective-blocking-of-tnf-receptor-1-attenuates-peritoneal-dialysis-fluid-induced-inflammation-of-the-peritoneum-in-mice
#17
Florian Kälble, Janine Damaske, Danijela Heide, Iris Arnold, Fabian Richter, Olaf Maier, Ulrich Eisel, Peter Scheurich, Klaus Pfizenmaier, Martin Zeier, Vedat Schwenger, Julia Ranzinger
Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of peritoneal tissue integrity. The resulting structural and functional reorganization of the peritoneal membrane diminishes ultrafiltration rate and thereby enhances mortality by limiting dialysis effectiveness over time. Tumour necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are key players during inflammatory processes. To date, the role of TNFR1 in peritoneal tissue damage during PD-treatment is completely undefined...
2016: PloS One
https://www.readbyqxmd.com/read/27754271/sy-17-1-dynamic-regulation-of-redox-regulating-factor-ape1-ref-1-on-the-oxidative-stress-and-vascular-inflammation
#18
Byeong Hwa Jeon
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that plays a central role in the cellular response to DNA damage and redox regulation against oxidative stress. APE1/Ref-1 is essential for cellular survival and embryonic lethal in knockout mouse models. Heterozygous APE1/Ref-1 mice showed impaired endothelium-dependent vasorelaxation, reduced vascular NO levels, and are hypertensive. APE1/Ref-1 reduces intracellular reactive oxygen species production by negatively regulating the activity of the NADPH oxidase...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27747245/tnf-%C3%AE-autocrine-feedback-loops-in-human-monocytes-the-pro-and-anti-inflammatory-roles-of-the-tnf-%C3%AE-receptors-support-the-concept-of-selective-tnfr1-blockade-in-vivo
#19
Jennie M Gane, Robert A Stockley, Elizabeth Sapey
Selective TNFR1 blockade in inflammatory diseases is emerging as a clinical strategy. We studied the roles of the two TNF-α receptors, TNFR1 and TNFR2, in human monocytes, the principal producer of TNF-α and central to many TNF-α driven diseases. We hypothesised that TNF-α has pro- and anti-inflammatory effects on monocytes, occurring differentially via TNFR1 and TNFR2. Monocytes were isolated from healthy human subjects and exposed to LPS, plus/minus the addition of blocking antibodies to TNF-α or its receptors...
2016: Journal of Immunology Research
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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