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https://www.readbyqxmd.com/read/28711499/inhibition-of-il-6-stat3-signaling-in-human-cancer-cells-using-evista
#1
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
#2
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
#3
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
#4
Stefan Rose-John
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. The 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, which 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28620096/interleukin-6-family-cytokines
#14
Stefan Rose-John
The interleukin (IL)-6 family cytokines is a group of cytokines consisting of IL-6, IL-11, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine (CLC), and IL-27. They are grouped into one family because the receptor complex of each cytokine contains two (IL-6 and IL-11) or one molecule (all others cytokines) of the signaling receptor subunit gp130. IL-6 family cytokines have overlapping but also distinct biologic activities and are involved among others in the regulation of the hepatic acute phase reaction, in B-cell stimulation, in the regulation of the balance between regulatory and effector T cells, in metabolic regulation, and in many neural functions...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28619247/childhood-maltreatment-severity-is-associated-with-elevated-c-reactive-protein-and-body-mass-index-in-adult-with-schizophrenia-and-bipolar-diagnoses
#15
Monica Aas, Ingrid Dieset, Sigrun Hope, Eva Hoseth, Ragni Mørch, Elina Reponen, Nils Eiel Steen, Jannicke F Anderssen, Thor Ueland, Pål Aukrust, Ingrid Agartz, Ole A Andreassen, Ingrid Melle
BACKGROUND: Several studies have described an association between childhood maltreatment and inflammatory markers in the psychotic disorders (schizophrenia [SZ] and bipolar disorder [BD]). Previous studies have been relatively small (<50 participants), and the severity of abuse and the putative influence of body mass index (BMI) have not been properly investigated. METHODS: The combined effects of childhood abuse severity and clinical diagnosis on inflammatory markers were investigated in a large sample (n=483) of patients with a disorder on the psychosis spectrum and in healthy controls (HCs)...
June 12, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28591717/peretinoin-an-acyclic-retinoid-suppresses-steatohepatitis-and-tumorigenesis-by-activating-autophagy-in-mice-fed-an-atherogenic-high-fat-diet
#16
Hikari Okada, Riuta Takabatake, Masao Honda, Kai Takegoshi, Taro Yamashita, Mikiko Nakamura, Takayoshi Shirasaki, Yoshio Sakai, Tetsuro Shimakami, Naoto Nagata, Toshinari Takamura, Takuji Tanaka, Shuichi Kaneko
The pathogenesis of non-alcoholic steatohepatitis (NASH) is still unclear and the prevention of the development of hepatocellular carcinoma (HCC) has not been established. We established an atherogenic and high-fat diet mouse model that develops hepatic steatosis, inflammation, fibrosis, and liver tumors at a high frequency. Using two NASH-HCC mouse models, we showed that peretinoin, an acyclic retinoid, significantly improved liver histology and reduced the incidence of liver tumors. Interestingly, we found that peretinoin induced autophagy in the liver of mice, which was characterized by the increased co-localized expression of microtubule-associated protein light chain 3B-II and lysosome-associated membrane protein 2, and increased autophagosome formation and autophagy flux in the liver...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28585906/elevation-of-plasma-oncostatin-m-in-heart-failure
#17
Damien Gruson, Benjamin Ferracin, Sylvie A Ahn, Michel F Rousseau
AIM: Oncostatin M (OSM) is an inflammatory cytokine of the gp130 family. OSM could participate in adverse cardiovascular remodeling through regulation of FGF23. MATERIALS & METHODS: OSM levels were determined in 80 heart failure patients with reduced left ventricular ejection fraction (HFrEF). RESULTS: OSM levels are significantly increased in HFrEF patients compared with healthy subjects. We have also demonstrated that, in HFrEF patients, plasma OSM levels are correlated to parathyroid hormone PTH(1-84) and 1,25(OH)2D, two other biomarkers related to bone and mineral metabolism and associated to adverse cardiovascular outcomes...
June 6, 2017: Future Cardiology
https://www.readbyqxmd.com/read/28557957/plasma-exosomes-from-hla-sensitized-kidney-transplant-recipients-contain-mrna-transcripts-which-predict-development-of-antibody-mediated-rejection
#18
Hao Zhang, Edmund Huang, Joseph Kahwaji, Cynthia C Nast, Ping Li, James Mirocha, David L Thomas, Shili Ge, Ashley A Vo, Stanley C Jordan, Mieko Toyoda
BACKGROUND: Sensitization to human leukocyte antigens (HLA) remains a significant immunologic barrier to successful transplantation. Identifying immune mechanisms responsible for antibody-mediated rejection (ABMR) is an important goal. Here we explored the possibility of predicting the risk for ABMR by measuring mRNA transcripts of ABMR-associated genes in plasma exosomes from kidney transplant patients. METHODS: Total RNA was extracted from exosomes purified from 152 EDTA-plasma samples of 64 patients (18 ABMR, 8 cell-mediated rejection [CMR], 38 no rejection in desensitized (DES) and non-desensitized (non-DES) control groups) for reverse transcription into cDNA, preamplification and then real time quantitative polymerase chain reaction (qPCR) for 21 candidate genes...
May 27, 2017: Transplantation
https://www.readbyqxmd.com/read/28532843/expression-and-regulation-of-interleukin-6-and-its-receptor-at-the-maternal-conceptus-interface-during-pregnancy-in-pigs
#19
Inkyu Yoo, Jisoo Han, Minjeong Kim, Hwanhee Jang, Soojin Sa, Sun-Ho Choi, Hakhyun Ka
It has been well established that interleukin 6 (IL6), a pleiotropic cytokine with multiple functional roles, is widely expressed in the female reproductive tract and mediates blastocyst implantation and placental development in many species. Uterine expression of IL6 during early pregnancy has been studied in pigs, but expression and function of IL6 at the maternal-placental interface throughout pregnancy have not been determined. Thus, we examined expression of IL6 and its receptors, IL6 receptor (IL6R) and GP130, in the uterine endometrium on Days 12 and 15 of the estrous cycle, and Days 12, 15, 30, 60, 90, and 114 of pregnancy, conceptus on Days 12 and 15, and chorioallantoic tissues on Days 30, 60, 90, and 114 of pregnancy in pigs...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28521720/the-role-of-il-27-and-its-receptor-in-the-pathogenesis-of-hiv-aids-and-anti-viral-immune-response
#20
Yu-Huang Zheng, Shui-Ling Xiao, Bo He, Yan He, Hua-Ying Zhou, Zi Chen, Mei He, Hong-Yan Wang, Yi-He Lin, Jing Cao
BACKGROUND: Cytokines have been widely demonstrated to involve in the pathogenesis of AIDS and the mechanisms of antiretroviral therapy. Interleukin 27 (IL-27) is a new member of the IL-12 cytokine family and has been shown to interfere HIV-1 virus replication with controversial findings. This study is to investigate the dynamic changes in plasma IL-27 level and cell surface IL-27 receptor expression in HIV/AIDS patients who underwent HAART. METHODS: Whole blood was collected from 34 HIV-positive/AIDS patients 0, 6, and 12 months after initiation of HAART and 27 healthy subjects...
May 17, 2017: Current HIV Research
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