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https://www.readbyqxmd.com/read/28820066/mutational-impact-on-the-interaction-between-human-il27-and-gp130-in-silico-approach-for-defending-hiv-infection
#1
Arundhati Banerjee, Rakhi Dasgupta, Sujay Ray
INTRODUCTION: With advances in proteomics, it is essential to investigate the molecular-level participation of IL27 and gp130 to hinder HIV infection. Their interaction causes cell-cycle arrest in HIV+ cells by activating the receptor-associated JAK signaling and causing apoptosis of cancerous cells. METHODOLOGY: The best human wild-type WT_IL27 model was prepared after varied molecular modeling techniques. The vital tyrosine residues in WT_IL27 were identified, mutated and IL27 was re-modeled...
August 17, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28783170/loss-of-claudin-3-expression-induces-il6-gp130-stat3-signaling-to-promote-colon-cancer-malignancy-by-hyperactivating-wnt-%C3%AE-catenin-signaling
#2
R Ahmad, B Kumar, Z Chen, X Chen, D Müller, S M Lele, M K Washington, S K Batra, P Dhawan, A B Singh
The hyperactivated Wnt/β-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28768641/acute-myotube-protein-synthesis-regulation-by-il-6-related-cytokines
#3
Song Gao, J Larry Durstine, Ho-Jin Koh, Wayne E Carver, Norma Frizzell, James A Carson
IL-6 and LIF, members of the IL-6 family of cytokines, play recognized paradoxical roles in skeletal muscle mass regulation, being associated with both growth and atrophy. Overload or muscle contractions can induce a transient increase in muscle IL-6 and LIF expression, which has a regulatory role in muscle hypertrophy. However, the cellular mechanisms involved in this regulation have not been completely identified. The induction of mTORC1-dependent myofiber protein synthesis is an established regulator of muscle hypertrophy, but the involvement of the IL-6 family of cytokines in this process is poorly understood...
August 2, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28760993/interferon-%C3%AE-is-a-master-checkpoint-regulator-of-cytokine-induced-differentiation
#4
Zhao Zha, Felicitas Bucher, Anahita Nejatfard, Tianqing Zheng, Hongkai Zhang, Kyungmoo Yea, Richard A Lerner
Cytokines are protein mediators that are known to be involved in many biological processes, including cell growth, survival, inflammation, and development. To study their regulation, we generated a library of 209 different cytokines. This was used in a combinatorial format to study the effects of cytokines on each other, with particular reference to the control of differentiation. This study showed that IFN-γ is a master checkpoint regulator for many cytokines. It operates via an autocrine mechanism to elevate STAT1 and induce internalization of gp130, a common component of many heterodimeric cytokine receptors...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28755912/examination-of-pathways-involved-in-leukemia-inhibitory-factor-lif-induced-cell-growth-arrest-using-label-free-proteomics-approach
#5
Syed Azmal Ali, Gurjeet Kaur, Ashok Kumar Mohanty, Sudarshan Kumar
Leukemia inhibitory factor (LIF) is a multifunctional highly glycosylated protein, synthesized and secreted in various body tissues. Besides the abundance in multiple organs, the molecular mechanism underlying the LIF interactions for cell survival and polarity is poorly understood. In the present study, high-resolution LC-MS/MS based LFQ approach identified 2083 proteins with the overall PSM as 16,032. This proteomics data reviles that LIF promotes the AKT-mTOR signaling pathway. It induces cell growth arrest by an intracellular pathways loop to increase the half-life of the cell...
July 26, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28747427/a-biallelic-mutation-in-il6st-encoding-the-gp130-co-receptor-causes-immunodeficiency-and-craniosynostosis
#6
Tobias Schwerd, Stephen R F Twigg, Dominik Aschenbrenner, Santiago Manrique, Kerry A Miller, Indira B Taylor, Melania Capitani, Simon J McGowan, Elizabeth Sweeney, Astrid Weber, Liye Chen, Paul Bowness, Andrew Riordan, Andrew Cant, Alexandra F Freeman, Joshua D Milner, Steven M Holland, Natalie Frede, Miryam Müller, Dirk Schmidt-Arras, Bodo Grimbacher, Steven A Wall, E Yvonne Jones, Andrew O M Wilkie, Holm H Uhlig
Multiple cytokines, including interleukin 6 (IL-6), IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF), signal via the common GP130 cytokine receptor subunit. In this study, we describe a patient with a homozygous mutation of IL6ST (encoding GP130 p.N404Y) who presented with recurrent infections, eczema, bronchiectasis, high IgE, eosinophilia, defective B cell memory, and an impaired acute-phase response, as well as skeletal abnormalities including craniosynostosis. The p.N404Y missense substitution is associated with loss of IL-6, IL-11, IL-27, and OSM signaling but a largely intact LIF response...
July 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28726777/humanin-g-hng-protects-age-related-macular-degeneration-amd-transmitochondrial-arpe-19-cybrids-from-mitochondrial-and-cellular-damage
#7
Sonali Nashine, Pinchas Cohen, Marilyn Chwa, Stephanie Lu, Anthony B Nesburn, Baruch D Kuppermann, M Cristina Kenney
Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28711499/inhibition-of-il-6-stat3-signaling-in-human-cancer-cells-using-evista
#8
Wei Shi, Dan Yan, Chongqiang Zhao, Miaomiao Xiao, Yina Wang, Haiyan Ma, Tianshu Liu, Hua Qin, Cuntai Zhang, Chenglong Li, Jiayuh Lin, Sheng Li, Jiagao Lv, Li Lin
Persistent activation of IL-6/STAT3 signaling pathway has been frequently detected in human cancer including breast cancer, colon cancer and multiple myeloma. IL-6/STAT3 can be a promising target for cancer prevent and treatment. However, few STAT3 inhibitors with high efficiency, specificity and safety is available for present clinical cancer therapy. Evista (Raloxifene·HCl) is known as selective estrogen receptor modulator which has been used for the prevention and treatment of osteoporosis and was approved for reducing the risk of invasive breast cancer...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28684999/mechanism-of-action-of-selective-inhibitors-of-il-6-induced-stat3-pathway-in-head-and-neck-cancer-cell-lines
#9
Malabika Sen, Paul A Johnston, Netanya I Pollock, Kara DeGrave, Sonali C Joyce, Maria L Freilino, Yun Hua, Daniel P Camarco, David A Close, Donna M Huryn, Peter Wipf, Jennifer R Grandis
Studies indicate that elevated interleukin-6 (IL-6) levels engage IL6Rα-gp130 receptor complexes to activate signal transducer and activator of transcription 3 (STAT3) that is hyperactivated in many cancers including head and neck squamous cell carcinoma (HNSCC). Our previous HCS campaign identified several hits that selectively blocked IL-6-induced STAT3 activation. This study describes our investigation of the mechanism(s) of action of three of the four chemical series that progressed to lead activities: a triazolothiadiazine (864669), amino alcohol (856350), and an oxazole-piperazine (4248543)...
July 2017: Journal of Chemical Biology
https://www.readbyqxmd.com/read/28677505/oncostatin-m-potential-implications-for-malignancy-and-metabolism
#10
Jacqueline M Stephens, Carrie M Elks
BACKGROUND: The gp130 cytokine, oncostatin M (OSM), serves several physiological and pathological functions. At the molecular level, OSM can directly or indirectly participate in tumorigenesis and insulin resistance development. Although OSM was initially found to be anti-proliferative in tumors, numerous tumorigenic roles for OSM have been reported in a variety of cancers. In metabolic diseases, OSM signaling may be required for homeostasis in both the liver and the adipose tissue, since abrogation of OSM signaling causes obesity, hepatic steatosis, and insulin resistance...
July 4, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28675418/the-soluble-interleukin-6-receptor-advanced-therapeutic-options-in-inflammation
#11
Stefan Rose-John
Interleukin (IL)-6 binds to IL-6R and the complex of IL-6 and IL-6R associates with the receptor subunit gp130, which initiates signaling. gp130 is expressed on all cells. IL-6R is cleaved by the ADAM17, generating a soluble IL-6R (sIL-6R). The sIL-6R binds IL-6 and the complex of IL-6 and sIL-6R binds to gp130 even on cells that do not express IL-6R. This process, which has been called IL-6 trans-signaling, increases the spectrum of target cells for IL-6. We generated a protein, sgp130Fc, which inhibits IL-6 trans-signaling without affecting IL-6 classic signaling...
July 4, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28672024/repositioning-bazedoxifene-as-a-novel-il-6-gp130-signaling-antagonist-for-human-rhabdomyosarcoma-therapy
#12
Hui Xiao, Hemant Kumar Bid, Xiang Chen, Xiaojuan Wu, Jia Wei, Yang Bian, Chengguang Zhao, Huameng Li, Chenglong Li, Jiayuh Lin
Interleukins-6 (IL-6)/GP130 signaling pathway represents a promising target for cancer therapy due to its critical role in survival and progression of multiple types of cancer. We have identified Bazedoxifene, a Food and Drug Administration (FDA)-approved drug used for the prevention of postmenopausal osteoporosis, with novel function as inhibitor of IL-6/GP130 interaction. In this study, we investigate the effect of Bazedoxifene in rhabdomyosarcoma and evaluate whether inhibiting IL-6/GP130 signaling is an effective therapeutic strategy for rhabdomyosarcoma...
2017: PloS One
https://www.readbyqxmd.com/read/28659496/secretion-of-interleukin-6-by-bone-marrow-mesenchymal-stem-cells-promotes-metastasis-in-hepatocellular-carcinoma
#13
Fei Mi, Liansheng Gong
Mesenchymal stem cells (MSCs) interact with tumor cells and regulate tumorigenesis and metastasis. As one of the important components of the tumor microenvironment, MSC-secreted cytokines play a critical role in cancer development. However, whether and how bone marrow MSCs (BMSCs) and their secreted cytokines participate in hepatocellular carcinoma (HCC) progression, still remains largely unknown. In the present study, we first measured the concentration of interleukin-6 (IL-6) in BMSC conditioned medium (BMSC-CM)...
June 28, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28659009/upregulation-of-interleukin-35-in-patients-with-endometriosis-stimulates-cell-proliferation
#14
Chun Zhang, Zheng Peng, DeYing Ban, Yi Zhang
In this study, we investigated the expression of interleukin 35 (IL-35) and its receptors in endometriosis, analyzed the function of IL-35 in primary culture model of endometrial stromal cells (ESCs), and evaluated their clinicapathological significance. Peripheral blood (PB) and peritoneal fluid (PF) were collected from 37 women with endometriosis and 24 control women. The ectopic endometrium was obtained from patients with endometriosis undergoing laparoscopic surgery. The eutopic and normal endometrium were collected by endometrial biopsy...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28645526/injury-induced-gp130-cytokine-signaling-in-peripheral-ganglia-is-reduced-in-diabetes-mellitus
#15
Jon P Niemi, Angela R Filous, Alicia DeFrancesco, Jane A Lindborg, Nisha A Malhotra, Gina N Wilson, Bowen Zhou, Samuel D Crish, Richard E Zigmond
Neuropathy is a major diabetic complication. While the mechanism of this neuropathy is not well understood, it is believed to result in part from deficient nerve regeneration. Work from our laboratory established that gp130 family of cytokines are induced in animals after axonal injury and are involved in the induction of regeneration-associated genes (RAGs) and in the conditioning lesion response. Here, we examine whether a reduction of cytokine signaling occurs in diabetes. Streptozotocin (STZ) was used to destroy pancreatic β cells, leading to chronic hyperglycemia...
June 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28645275/rapid-monocyte-infiltration-following-retinal-detachment-is-dependent-on-non-canonical-il6-signaling-through-gp130
#16
Xinlei Wang, Eric B Miller, Mayank Goswami, Pengfei Zhang, Kaitryn E Ronning, Sarah J Karlen, Robert J Zawadzki, Edward N Pugh, Marie E Burns
BACKGROUND: Retinal detachment (RD) can lead to proliferative vitreoretinopathy (PVR), a leading cause of intractable vision loss. PVR is associated with a cytokine storm involving common proinflammatory molecules like IL6, but little is known about the source and downstream signaling of IL6 and the consequences for the retina. Here, we investigated the early immune response and resultant cytokine signaling following RD in mice. METHODS: RD was induced in C57BL/6 J and IL6 knockout mice, and the resulting inflammatory response was examined using immunohistochemistry and flow cytometry...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28642760/interleukin-6-in-allogeneic-stem-cell-transplantation-its-possible-importance-for-immunoregulation-and-as-a-therapeutic-target
#17
REVIEW
Tor Henrik Anderson Tvedt, Elisabeth Ersvaer, Anders Aune Tveita, Øystein Bruserud
Allogeneic stem cell transplantation is associated with a high risk of treatment-related mortality mainly caused by infections and graft-versus-host disease (GVHD). GVHD is characterized by severe immune dysregulation and impaired regeneration of different tissues, i.e., epithelial barriers and the liver. The balance between pro- and anti-inflammatory cytokine influences the risk of GVHD. Interleukin-6 (IL-6) is a cytokine that previously has been associated with pro-inflammatory effects. However, more recent evidence from various autoimmune diseases (e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28632778/over-expressing-the-soluble-gp130-fc-does-not-ameliorate-methionine-and-choline-deficient-diet-induced-non-alcoholic-steatohepatitis-in-mice
#18
Helene L Kammoun, Tamara Louise Allen, Darren Colin Henstridge, Michael James Kraakman, Lone Peijs, Stefan Rose-John, Mark Anthony Febbraio
Non-alcoholic steatohepatitis (NASH) is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6) has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice) fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet) and hypothesized that markers of NASH would be ameliorated in such mice...
2017: PloS One
https://www.readbyqxmd.com/read/28630024/proteolytic-control-of-interleukin-11-and-interleukin-6-biology
#19
REVIEW
Juliane Lokau, Maria Agthe, Charlotte M Flynn, Christoph Garbers
Interleukin-11 (IL-11) and IL-6 are secreted glycoproteins which fulfill important homeostatic functions. Activation of target cells occurs via membrane-bound IL-11 and IL-6 receptors (IL-11R and IL-6R, respectively). Formation of IL-11/IL-11R and IL-6/IL-6R complexes triggers the recruitment of a homodimer of the ubiquitously expressed signal-transducing β-receptor gp130 (classic signaling). IL-11R and IL-6R can be shed by several proteases, albeit with different preferences and specificities, and these soluble receptors (sIL-11R and sIL-6R) act as agonists and can activate in principle all cells via gp130...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28620241/tgf-beta-atra-induced-tregs-express-a-selected-set-of-micrornas-involved-in-the-repression-of-transcripts-related-to-th17-differentiation
#20
Josiane Lilian Dos Santos Schiavinato, Rodrigo Haddad, Felipe Saldanha-Araujo, João Baiochi, Amélia Goes Araujo, Priscila Santos Scheucher, Dimas Tadeu Covas, Marco Antonio Zago, Rodrigo Alexandre Panepucci
Regulatory T cells (Tregs) are essential regulators of immune tolerance. atRA and TGF-β can inhibit the polarization of naïve T cells into inflammatory Th17 cells, favoring the generation of stable iTregs, however the regulatory mechanisms involved are not fully understood. In this context, the roles of individual microRNAs in Tregs are largely unexplored. Naïve T cells were immunomagnetically isolated from umbilical cord blood and activated with anti-human CD2/CD3/CD28 beads in the presence of IL-2 alone (CD4Med) or with the addition of TGF-β and atRA (CD4TGF/atRA)...
June 15, 2017: Scientific Reports
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