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https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#1
Yina Wang, Haiyan Ma, Chongqiang Zhao, Tianshu Liu, Dan Yan, David Jou, Huameng Li, Cuntai Zhang, Jiagao Lü, Chenglong Li, Jiayuh Lin, Sheng Li, Li Lin
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407804/mathematical-model-of-tgf-%C3%AE-signalling-feedback-coupling-is-consistent-with-signal-switching
#2
Shabnam Khatibi, Hong-Jian Zhu, John Wagner, Chin Wee Tan, Jonathan H Manton, Antony W Burgess
BACKGROUND: Transforming growth factor β (TGF-β) signalling regulates the development of embryos and tissue homeostasis in adults. In conjunction with other oncogenic changes, long-term perturbation of TGF-β signalling is associated with cancer metastasis. Although TGF-β signalling can be complex, many of the signalling components are well defined, so it is possible to develop mathematical models of TGF-β signalling using reduction and scaling methods. The parameterization of our TGF-β signalling model is consistent with experimental data...
April 13, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28402851/il-6-improves-energy-and-glucose-homeostasis-in-obesity-via-enhanced-central-il-6-trans-signaling
#3
Katharina Timper, Jesse Lee Denson, Sophie Marie Steculorum, Christian Heilinger, Linda Engström-Ruud, Claudia Maria Wunderlich, Stefan Rose-John, F Thomas Wunderlich, Jens Claus Brüning
Interleukin (IL)-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R) expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28363692/il-6-signaling-in-diabetic-nephropathy-from-pathophysiology-to-therapeutic-perspectives
#4
Eva Feigerlová, Shyue-Fang Battaglia-Hsu
Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD). Interleukin-6 (IL-6) signaling participates in inflammation responses central to the progression of DN. Current evidence suggests that these IL-6 responses are mediated via gp130-STAT3 dependent mechanisms which, on one hand, trigger globally the transition from innate to adaptive immune response, and on the other hand act locally for tissue remodeling and immune cell infiltration. In diabetic conditions the role of IL-6 is not well elucidated...
March 23, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28356514/cytokine-receptor-signaling-is-required-for-the-survival-of-alk-anaplastic-large-cell-lymphoma-even-in-the-presence-of-jak1-stat3-mutations
#5
Jing Chen, Yong Zhang, Michael N Petrus, Wenming Xiao, Alina Nicolae, Mark Raffeld, Stefania Pittaluga, Richard N Bamford, Masao Nakagawa, Sunny Tianyi Ouyang, Alan L Epstein, Marshall E Kadin, Annarose Del Mistro, Richard Woessner, Elaine S Jaffe, Thomas A Waldmann
Activating Janus kinase (JAK) and signal transducer and activator of transcription (STAT) mutations have been discovered in many T-cell malignancies, including anaplastic lymphoma kinase (ALK)(-) anaplastic large cell lymphomas (ALCLs). However, such mutations occur in a minority of patients. To investigate the clinical application of targeting JAK for ALK- ALCL, we treated ALK- cell lines of various histological origins with JAK inhibitors. Interestingly, most exogenous cytokine-independent cell lines responded to JAK inhibition regardless of JAK mutation status...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28338646/type-iv-secretion-and-signal-transduction-of-helicobacter-pylori-caga-through-interactions-with-host-cell-receptors
#6
REVIEW
Steffen Backert, Nicole Tegtmeyer
Helicobacter pylori is a highly successful human bacterium, which is exceptionally equipped to persistently inhabit the human stomach. Colonization by this pathogen is associated with gastric disorders ranging from chronic gastritis and peptic ulcers to cancer. Highly virulent H. pylori strains express the well-established adhesins BabA/B, SabA, AlpA/B, OipA, and HopQ, and a type IV secretion system (T4SS) encoded by the cag pathogenicity island (PAI). The adhesins ascertain intimate bacterial contact to gastric epithelial cells, while the T4SS represents an extracellular pilus-like structure for the translocation of the effector protein CagA...
March 24, 2017: Toxins
https://www.readbyqxmd.com/read/28315013/protective-vaccination-and-blood-stage-malaria-modify-dna-methylation-of-gene-promoters-in-the-liver-of-balb-c-mice
#7
Saleh Al-Quraishy, Mohamed A Dkhil, Abdel-Azeem S Abdel-Baki, Foued Ghanjati, Lars Erichsen, Simeon Santourlidis, Frank Wunderlich, Marcos J Araúzo-Bravo
Epigenetic mechanisms such as DNA methylation are increasingly recognized to be critical for vaccination efficacy and outcome of different infectious diseases, but corresponding information is scarcely available for host defense against malaria. In the experimental blood-stage malaria Plasmodium chabaudi, we investigate the possible effects of a blood-stage vaccine on DNA methylation of gene promoters in the liver, known as effector against blood-stage malaria, using DNA methylation microarrays. Naturally susceptible Balb/c mice acquire, by protective vaccination, the potency to survive P...
March 18, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28297588/oncostatin-m-preconditioned-mesenchymal-stem-cells-alleviate-bleomycin-induced-pulmonary-fibrosis-through-paracrine-effects-of-the-hepatocyte-growth-factor
#8
Ying-Wei Lan, Si-Min Theng, Tsung-Teng Huang, Kong-Bung Choo, Chuan-Mu Chen, Han-Pin Kuo, Kowit-Yu Chong
Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28297566/instructive-role-of-the-microenvironment-in-preventing-renal-fibrosis
#9
Kei Matsumoto, Sandhya Xavier, Jun Chen, Yujiro Kida, Mark Lipphardt, Reina Ikeda, Annie Gevertz, Mario Caviris, Antonis K Hatzopoulos, Ivo Kalajzic, James Dutton, Brian B Ratliff, Hong Zhao, Zbygniew Darzynkiewicz, Stefan Rose-John, Michael S Goligorsky
Accumulation of myofibroblasts is a hallmark of renal fibrosis. A significant proportion of myofibroblasts has been reported to originate via endothelial-mesenchymal transition. We initially hypothesized that exposing myofibroblasts to the extract of endothelial progenitor cells (EPCs) could reverse this transition. Indeed, in vitro treatment of transforming growth factor-β1 (TGF-β1)-activated fibroblasts with EPC extract prevented expression of α-smooth muscle actin (α-SMA); however, it did not enhance expression of endothelial markers...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28294559/the-platelet-activating-receptor-c-type-lectin-receptor-2-plays-an-essential-role-in-liver-regeneration-after-partial-hepatectomy-in-mice
#10
H Kono, H Fujii, K Suzuki-Inoue, O Inoue, S Furuya, K Hirayama, Y Akazawa, Y Nakata, C Sun, N Tsukiji, T Shirai, Y Ozaki
Essentials Regeneration role of C-type lectin receptor-2 (CLEC-2) after 70% hepatectomy (HPx) was investigated. Wild-type or CLEC-2 deleted from platelets of chimeric mice (flKO) underwent HPx. The liver/body weight ratio was significantly lower in the flKO than in the wild-type. CLEC-2 plays an essential role in liver regeneration after HPx. SUMMARY: Background and aim The aim of the present study was to investigate the role of C-type lectin receptor (CLEC)-2 in liver regeneration following partial liver resection in mice...
March 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28289419/cytokine-signatures-in-mucocutaneous-and-ocular-beh%C3%A3-et-s-disease
#11
Giuseppe Lopalco, Orso Maria Lucherini, Antonio Lopalco, Vincenzo Venerito, Claudia Fabiani, Bruno Frediani, Mauro Galeazzi, Giovanni Lapadula, Luca Cantarini, Florenzo Iannone
Behçet's disease (BD) is a multi-systemic inflammatory disorder consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis; however, many other organs may be affected. Several pro-inflammatory cytokines, mainly derived from Th1 and Th17 lymphocytes, seem to be involved in different pathogenic pathways leading to development of the clinical manifestations. On this basis, the primary aim of our study was to compare a core set of pro-inflammatory cytokines between patients with BD and healthy control (HC)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28270211/syndecan-1-is-a-novel-molecular-marker-for-triple-negative-inflammatory-breast-cancer-and-modulates-the-cancer-stem-cell-phenotype-via-the-il-6-stat3-notch-and-egfr-signaling-pathways
#12
Sherif Abdelaziz Ibrahim, Ramy Gadalla, Eslam A El-Ghonaimy, Omnia Samir, Hossam Taha Mohamed, Hebatallah Hassan, Burkhard Greve, Mohamed El-Shinawi, Mona Mostafa Mohamed, Martin Götte
BACKGROUND: Inflammatory breast cancer (IBC), a particularly aggressive form of breast cancer, is characterized by cancer stem cell (CSC) phenotype. Due to a lack of targeted therapies, the identification of molecular markers of IBC is of major importance. The heparan sulfate proteoglycan Syndecan-1 acts as a coreceptor for growth factors and chemokines, modulating inflammation, tumor progression, and cancer stemness, thus it may emerge as a molecular marker for IBC. METHODS: We characterized expression of Syndecan-1 and the CSC marker CD44, Notch-1 & -3 and EGFR in carcinoma tissues of triple negative IBC (n = 13) and non-IBC (n = 17) patients using qPCR and immunohistochemistry...
March 7, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28265003/sorla-in-interleukin-6-signaling-and-turnover
#13
Jakob Vejby Larsen, Claus Munck Petersen
Interleukin-6 (IL-6) is a multifunctional cytokine with important functions in various physiologic processes. Mice lacking IL-6 exhibit multiple phenotypic abnormalities such as an inadequate immune and acute-phase response, and elevated levels of circulating IL-6 have been found to accompany several pathologic conditions. IL-6 binds the non-signaling IL-6 receptor (IL-6R) - which is expressed as a transmembrane, as well as a secreted circulating protein - before it engages homodimeric gp130 for signaling. Complex-formation between IL-6 and the membrane-bound IL-6 receptor gives rise to classic cis-signaling, whereas complex-formation between IL-6 and the soluble IL-6R results in trans-signaling...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28255340/phenytoin-silver-a-new-nanocompound-for-promoting-dermal-wound-healing-via-comprehensive-pharmacological-action
#14
Xiao-Yu Ai, Hui-Juan Liu, Cheng Lu, Cai-Li Liang, Yan Sun, Shuang Chen, Bo Sun, Yang Li, Yan-Rong Liu, Qiang Zhang, Xue-Qiang Liu, Ting Xiao, Xue-Shuang Jing, Tao Sun, Hong-Gang Zhou, Cheng Yang
Phenytoin, an antiepileptic drug, has been widely used for wound healing. Inspired by previous studies, phenytoin silver (PnAg), a sparingly soluble silver nanocompound, was synthesized which exhibited good therapeutic efficacy in tissue repair with low toxicity (LD50 >5 g/kg). In vivo studies showed that PnAg could accelerate dermal wound healing and strong inflammation control in Sprague-Dawley rats (SD rat) and Bama minipigs. Due to its low solubility, PnAg led to low toxicity and blood enrichment in animals...
2017: Theranostics
https://www.readbyqxmd.com/read/28255204/dual-roles-of-il-27-in-cancer-biology-and-immunotherapy
#15
REVIEW
Marina Fabbi, Grazia Carbotti, Silvano Ferrini
IL-27 is a pleiotropic two-chain cytokine, composed of EBI3 and IL-27p28 subunits, which is structurally related to both IL-12 and IL-6 cytokine families. IL-27 acts through a heterodimer receptor consisting of IL-27Rα (WSX1) and gp130 chains, which mediate signaling predominantly through STAT1 and STAT3. IL-27 was initially reported as an immune-enhancing cytokine that supports CD4(+) T cell proliferation, T helper (Th)1 cell differentiation, and IFN-γ production, acting in concert with IL-12. However, subsequent studies demonstrated that IL-27 displays complex immune-regulatory functions, which may result in either proinflammatory or anti-inflammatory effects in relationship to the biological context and experimental models considered...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28250574/interleukin-6-trans-signaling-and-ischemic-vascular-disease-the-important-role-of-soluble-gp130
#16
REVIEW
Mario Luca Morieri, Angelina Passaro, Giovanni Zuliani
Inflammation plays a major role in the onset of cardiovascular disease (CVD). Interleukine-6 (IL-6) is a multifunctional cytokine involved both in the beneficial acute inflammatory response and in the detrimental chronic low-grade systemic inflammation. Large genetic human studies, using Mendelian randomization approaches, have clearly showed that IL-6 pathway is causally involved in the onset of myocardial infarction. At the same time, IL-6 pathway is divided into two arms: classic signaling (effective in hepatocytes and leukocytes) and trans-signaling (with ubiquitous activity)...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28241173/jak1-genomic-alteration-associated-with-exceptional-response-to-siltuximab-in-cutaneous-castleman-disease
#17
Maulik Patel, Sadakatsu Ikeda, Susan R Pilat, Razelle Kurzrock
Importance: Castleman disease (CD) is an ultrarare, interleukin-6 (IL-6)-driven lymphoproliferative disorder whose underlying molecular alterations are unknown. Siltuximab (anti-IL-6 antibody) is approved for treatment of this disease. To our knowledge, genomic sequencing of CD has not been reported. Objective: To investigate and identify molecular aberration(s) that help explain the exceptional response to siltuximab in a patient with cutaneous CD. Design, Setting, and Participants: This case study examines data from comprehensive genomic profiling (using targeted next-generation sequencing) of tissue from a patient with cutaneous CD who demonstrated an exceptional response to siltuximab treated at a National Cancer Institute-designated Comprehensive Cancer Center...
February 22, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28160627/interleukin-11-driven-gastric-tumourigenesis-is-independent-of-trans-signalling
#18
Jesse J Balic, Christoph Garbers, Stefan Rose-John, Liang Yu, Brendan J Jenkins
Deregulated gp130-dependent STAT3 signalling by the pleiotropic cytokine interleukin (IL)-11 has been implicated in the pathogenesis of gastric cancer (GC), the third most common cancer worldwide. While the IL-11-gp130-STAT3 signalling axis has traditionally been thought to exclusively use the membrane-bound IL-11 receptor (mIL-11R), recent evidence suggests that mIL-11R can be proteolytically cleaved to generate a soluble form (sIL-11R) which can elicit trans-signalling. Since the role of IL-11 trans-signalling in disease pathogenesis is unknown, here we have employed the IL-11-driven gp130(F/F) spontaneous model of GC to determine whether IL-11 trans-signalling promotes gastric tumourigenesis...
February 1, 2017: Cytokine
https://www.readbyqxmd.com/read/28159554/trans-signaling-of-interleukin-6-il-6-is-mediated-by-the-soluble-il-6-receptor-but-not-by-soluble-cd5
#19
Samadhi Aparicio-Siegmund, Malte Deseke, Annett Lickert, Christoph Garbers
IL-6 exerts its pleiotropic activities on its target cells via the IL-6 alpha-receptor (IL-6R), which is expressed on a limited number of cell types. IL-6 can further signal via soluble forms of its receptor (sIL-6R), a process that has been termed trans-signaling. Recently, CD5 was described as an alternative alpha-receptor for IL-6 on B cells leading to the phosphorylation of the transcription factor STAT3 via the signal-transducing β-receptor gp130 in a Jak2-dependent manner. In this study, we sought to investigate whether IL-6 was also able to signal via soluble CD5 (sCD5) analogous to IL-6 trans-signaling...
January 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28130546/yap-il-6st-autoregulatory-loop-activated-on-apc-loss-controls-colonic-tumorigenesis
#20
Koji Taniguchi, Toshiro Moroishi, Petrus R de Jong, Michal Krawczyk, Britta Moyo Grebbin, Huiyan Luo, Rui-Hua Xu, Nicole Golob-Schwarzl, Caroline Schweiger, Kepeng Wang, Giuseppe Di Caro, Ying Feng, Eric R Fearon, Eyal Raz, Lukas Kenner, Henner F Farin, Kun-Liang Guan, Johannes Haybaeck, Christian Datz, Kang Zhang, Michael Karin
Loss of tumor suppressor adenomatous polyposis coli (APC) activates β-catenin to initiate colorectal tumorigenesis. However, β-catenin (CTNNB1) activating mutations rarely occur in human colorectal cancer (CRC). We found that APC loss also results in up-regulation of IL-6 signal transducer (IL-6ST/gp130), thereby activating Src family kinases (SFKs), YAP, and STAT3, which are simultaneously up-regulated in the majority of human CRC. Although, initial YAP activation, which stimulates IL6ST gene transcription, may be caused by reduced serine phosphorylation, sustained YAP activation depends on tyrosine phosphorylation by SFKs, whose inhibition, along with STAT3-activating JAK kinases, causes regression of established colorectal tumors...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
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