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https://www.readbyqxmd.com/read/29207075/blocking-interleukin-6-signaling-inhibits-cell-viability-proliferation-glycolysis-and-colony-forming-activity-of-human-medulloblastoma-cells
#1
Xiang Chen, Jia Wei, Chenglong Li, Christopher R Pierson, Jonathan L Finlay, Jiayuh Lin
Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL‑6) have tumor-promoting activity and are associated with poor survival outcomes in many cancers. Additionally, the IL‑6/GP130/STAT3 axis has been widely studied due to its pivotal role in tumor development and maintenance in a number of tissue types, including the cerebellum. However, the connection between IL‑6 signaling and medulloblastoma progression is largely unexplored. In the present study, we observed that IL‑6 induced medulloblastoma cell viability, cell proliferation and glycolysis...
November 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29195127/rapamycin-synergizes-with-cisplatin-in-antiendometrial-cancer-activation-by-improving-il-27-stimulated-cytotoxicity-of-nk-cells
#2
Wen-Jie Zhou, Kai-Kai Chang, Ke Wu, Hui-Li Yang, Jie Mei, Feng Xie, Da-Jin Li, Ming-Qing Li
Natural killer (NK) cell function is critical for controlling initial tumor growth and determining chemosensitivity of the tumor. A synergistic relationship between rapamycin and cisplatin in uterine endometrial cancer (UEC) in vitro has been reported, but the mechanism and the combined therapeutic strategy for endometrial cancer (EC) are still unknown. We found a positive correlation between the level of IL-27 and the differentiated stage of UEC. The increase of IL-27 in uterine endometrial cancer cell (UECC) lines (Ishikawa, RL95-2 and KLE) led to a high cytotoxic activity of NK cells to UECC in the co-culture system...
November 28, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29191994/correction-for-cousins-and-nicholas-role-of-human-herpesvirus-8-interleukin-6-activated-gp130-signal-transducer-in-primary-effusion-lymphoma-cell-growth-and-viability
#3
Emily Cousins, John Nicholas
No abstract text is available yet for this article.
December 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29186034/cellular-and-oxidative-mechanisms-associated-with-interleukin-6-signaling-in-the-vasculature
#4
REVIEW
Sean P Didion
Reactive oxygen species, particularly superoxide, promote endothelial dysfunction and alterations in vascular structure. It is increasingly recognized that inflammatory cytokines, such as interleukin-6 (IL-6), contribute to endothelial dysfunction and vascular hypertrophy and fibrosis. IL-6 is increased in a number of cardiovascular diseases, including hypertension. IL-6 is also associated with a higher incidence of future cardiovascular events and all-cause mortality. Both immune and vascular cells produce IL-6 in response to a number of stimuli, such as angiotensin II...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29161500/a-small-molecule-mimetic-of-the-humanin-peptide-as-a-candidate-for-modulating-nmda-induced-neurotoxicity
#5
Mohammad Parvez Alam, Tina Bilousova, Patricia Spilman, Kanagasabai Vadivel, Dongsheng Bai, Denis Evseenko, Varghese John
Humanin (HN), a 24-amino acid bioactive peptide, has been shown to increase cell survival of neurons after exposure to Aβ and NMDA-induced toxicity and thus could be beneficial in the treatment of Alzheimer's disease (AD). The neuroprotection by HN is reported to be primarily through its agonist binding properties to the gp130 receptor. However, peptidic nature of HN presents challenges in its development as a therapeutic for AD. We report here for the first time the elucidation of the binding site of Humanin (HN) peptide to gp130 receptor extracellular domain through modeling and the synthesis of small molecule mimetics that interact with the HN binding site on the gp130 receptor that provides protection against NMDA-induced neurotoxicity in primary hippocampal neurons...
November 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29140406/smad3-stat3-crosstalk-in-pathophysiological-contexts
#6
Yuka Itoh, Masao Saitoh, Keiji Miyazawa
Smad3 and STAT3 are intracellular molecules that transmit signals from plasma membrane receptors to the nucleus. Smad3 operates downstream of growth/differentiation factors that utilize activin receptor-like kinase (ALK)-4, 5, or 7, such as transforming growth factor-β (TGF-β), activin, and myostatin. STAT3 principally functions downstream of cytokines that exert their effects via gp130 and Janus family kinases, including interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M. Accumulating evidence indicates that Smad3 and STAT3 engage in crosstalk in a highly context-dependent fashion, cooperating in some conditions while acting antagonistically each other in others...
November 13, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29138334/correction-for-cousins-et-al-human-herpesvirus-8-viral-interleukin-6-signaling-through-gp130-promotes-virus-replication-in-primary-effusion-lymphoma-and-endothelial-cells
#7
Emily Cousins, Yang Gao, Gordon Sandford, John Nicholas
No abstract text is available yet for this article.
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29123149/il-6-il-12-cytokine-receptor-shuffling-of-extra-and-intracellular-domains-reveals-canonical-stat-activation-via-synthetic-il-35-and-il-39-signaling
#8
D M Floss, M Schönberg, M Franke, F C Horstmeier, E Engelowski, A Schneider, E M Rosenfeldt, J Scheller
IL-35 and IL-39 are recently discovered shared members of the IL-6- and IL-12-type cytokine family with immune-suppressive capacity. IL-35 has been reported to induce the formation of four different receptor complexes: gp130:IL-12β2, gp130:gp130, IL-12β2:IL-12β2, and IL-12β2:WSX-1. IL-39 was proposed to form a gp130:IL-23R receptor complex. IL-35, but not IL-39, has been reported to activate non-conventional STAT signaling, depending on the receptor complex and target cell. Analyses of IL-35 and IL-39 are, however, hampered by the lack of biologically active recombinant IL-35 and IL-39 proteins...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29103443/protein-and-mrna-expressions-of-il-6-and-its-key-signaling-factors-under-orthodontic-forces-in-mice-an-in-vivo-study
#9
Yi Liu, Fang Song, Shu Wu, Shushu He, Mingmei Meng, Chunxiao Lv, Qingqing Yang, Song Chen
INTRODUCTION: The purpose of this study was to investigate the mechanical loading-induced changes in protein and mRNA expressions of interleukin-6 (IL-6) and its key signaling factors glycoprotein 130 (gp130), signal transducer and activator of transcription 3 (STAT3), and the Src homology phosphotyrosine phosphatase (SHP2) at the tension and compression sides of the teeth in mouse models. METHODS: A total of 55 C57B/6 mice (10 weeks old) were divided into 3 groups...
November 2017: American Journal of Orthodontics and Dentofacial Orthopedics
https://www.readbyqxmd.com/read/29066599/il-6-type-cytokine-signaling-in-adipocytes-induces-intestinal-glp-1-secretion
#10
Stephan Wueest, Céline I Laesser, Marianne Böni-Schnetzler, Flurin Item, Fabrizio C Lucchini, Marcela Borsigova, Werner Müller, Marc Y Donath, Daniel Konrad
We recently showed that IL-6-type cytokine signaling in adipocytes induces FFA release from visceral adipocytes thereby promoting obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type cytokines may increase the release of leptin from adipocytes and by that means induce GLP-1 secretion. We thus hypothesized that IL-6-type cytokine signaling in adipocytes may regulate insulin secretion. To this end, mice with adipocyte-specific knockout of gp130, the signal transducer protein of IL-6, were fed a high fat diet for 12 weeks...
October 24, 2017: Diabetes
https://www.readbyqxmd.com/read/29038846/a-possible-implication-of-reduced-levels-of-lif-lifr-and-gp130-in-vasculopathy-related-to-systemic-sclerosis
#11
Takashi Taniguchi, Takuya Miyagawa, Zenshiro Tamaki, Kouki Nakamura, Takashi Yamashita, Ryosuke Saigusa, Takehiro Takahashi, Tetsuo Toyama, Yohei Ichimura, Ayumi Yoshizaki, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato, Yoshihide Asano
Leukemia inhibitory factor (LIF) is a member of IL-6 family, which serves as a potent chemoattractant for neutrophils as well as a potent angiostatic factor. LIF has been implicated in various autoimmune inflammatory diseases, but its role still remains elusive in systemic sclerosis (SSc). Therefore, we investigated the potential role of LIF in the development of SSc by evaluating the clinical correlation of serum LIF levels, the expression of LIF and its receptors in skin samples, and in vitro experiments with human dermal microvascular endothelial cells...
October 16, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29038604/overexpression-of-osm-and-il-6-impacts-the-polarization-of-pro-fibrotic-macrophages-and-the-development-of-bleomycin-induced-lung-fibrosis
#12
Ehab A Ayaub, Anisha Dubey, Jewel Imani, Fernando Botelho, Martin R J Kolb, Carl D Richards, Kjetil Ask
Although recent evidence indicates that gp130 cytokines, Oncostatin M (OSM) and IL-6 are involved in alternative programming of macrophages, their role in lung fibrogenesis is poorly understood. Here, we investigated the effect of transient adenoviral overexpression of OSM or IL-6 in mice during bleomycin-induced lung fibrosis. Lung fibrosis and M2-like macrophage accumulation were assessed by immunohistochemistry, western blotting, gene expression and flow cytometry. Ex-vivo isolated alveolar and bone marrow-derived macrophages were examined for M2-like programming and signalling...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29020964/il-27-mediates-hla-class-i-up-regulation-which-can-be-inhibited-by-the-il-6-pathway-in-hla-deficient-small-cell-lung-cancer-cells
#13
Grazia Carbotti, Amin Reza Nikpoor, Paola Vacca, Rosaria Gangemi, Chiara Giordano, Francesco Campelli, Silvano Ferrini, Marina Fabbi
BACKGROUND: Recently, immunotherapy with anti-PD-1 antibodies has shown clinical benefit in recurrent Small Cell Lung Cancer (SCLC). Since anti-PD-1 re-activates anti-tumor Cytotoxic T Lymphocyte (CTL) responses, it is crucial to understand the mechanisms regulating HLA class I, and PD-L1 expression in HLA-negative SCLC. Here we addressed the role of IL-27, a cytokine related to both IL-6 and IL-12 families. METHODS: The human SCLC cell lines NCI-N592, -H69, -H146, -H446 and -H82 were treated in vitro with different cytokines (IL-27, IFN-γ, IL-6 or a soluble IL-6R/IL-6 chimera [sIL-6R/IL-6]) at different time points and analyzed for tyrosine-phosphorylated STAT proteins by Western blot, for surface molecule expression by immunofluorescence and FACS analyses or for specific mRNA expression by QRT-PCR...
October 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28989066/interleukin-35-expression-correlates-with-microvessel-density-in-pancreatic-ductal-adenocarcinoma-recruits-monocytes-and-promotes-growth-and-angiogenesis-of-xenograft-tumors-in-mice
#14
Chongbiao Huang, Zengxun Li, Na Li, Yang Li, Antao Chang, Tiansuo Zhao, Xiuchao Wang, Hongwei Wang, Song Gao, Shengyu Yang, Jihui Hao, He Ren
BACKGROUND & AIMS: Cells of the monocyte lineage contribute to tumor angiogenesis. Interleukin 35 (IL35) is a member of the IL12 family produced by regulatory, but not effector, T cells. IL35 is a dimer comprising the IL12 alpha and IL27 beta chains, encoded by IL12A and EBI3, respectively. Expression of IL35 is increased in pancreatic ductal adenocarcinomas (PDACs) compared with normal pancreatic tissues, and promotes metastasis. We investigated the role of IL-35 in monocyte-induced angiogenesis of PDAC in mice...
October 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28978005/bazedoxifene-enhances-the-anti-tumor-effects-of-cisplatin-and-radiation-treatment-by-blocking-il-6-signaling-in-head-and-neck-cancer
#15
Arti Yadav, Bhavna Kumar, Theodoros N Teknos, Pawan Kumar
Recent studies have shown that IL-6 signaling plays an important role in the aggressive and metastatic phenotype of head and neck squamous cell carcinoma (HNSCC). Therefore, we hypothesized that targeting of IL-6 signaling in HNSCC could enhance the therapeutic efficacy of standard chemoradiation treatment. We used both in vitro and in vivo models to test the efficacy of Bazedoxifene (BZA), a drug that was originally developed as a newer-generation selective estrogen receptor modulator (SERM) for the treatment of postmenopausal osteoporosis...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28964648/association-of-il6st-gp130-polymorphism-with-functional-outcome-following-spontaneous-intracerebral-hemorrhage
#16
Nada El Husseini, Benjamin M Hoffman, Ellen R Bennett, Yen-Wei Li, Rachel A Williamson Taylor, Claire E Hailey, Kara Richardson, Yi-Ju Li, Daniel T Laskowitz, Michael L James
BACKGROUND AND PURPOSE: Genes associated with the inflammatory response and cytostructural integrity may influence recovery following a brain injury. To examine this in the setting of spontaneous intracerebral hemorrhage (ICH), selected single nucleotide polymorphisms (SNPs) were assessed for associations with patient outcome. METHODS: A cohort of 54 patients with supratentorial ICH were enrolled. Based on known involvement with neuroinflammation and cytostructural integrity, 10 preselected SNPs from 6 candidate genes were tested for associations with 6-month functional outcome (modified Rankin Scale [mRS] ≥ 3), mortality, and in-hospital deterioration (Glasgow Coma Scale decrease by >2 within 7 days of admission) following ICH...
September 27, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28960206/mir-148a-inhibits-colitis-and-colitis-associated-tumorigenesis-in-mice
#17
Yahui Zhu, Li Gu, Yajun Li, Xi Lin, Hongxing Shen, Kaisa Cui, Li Chen, Feng Zhou, Qiu Zhao, Jinxiang Zhang, Bo Zhong, Edward Prochownik, Youjun Li
miR-148a has been shown to regulate inflammation, immunity and the growth of certain tumors, but its roles in colitis and colorectal tumorigenesis remain largely undetermined. Here we found miR-148a-deficient mice to be more susceptible to colitis and colitis-associated tumorigenesis. Both were associated with increased nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling. Bone marrow- and non-bone marrow-derived miR-148a contributed to colitis and colitis-associated tumorigenesis...
December 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28948853/tgf-%C3%AE-and-il-6-family-signalling-crosstalk-an-integrated-model
#18
Shabnam Khatibi, Jeff Babon, John Wagner, Jonathan H Manton, Chin Wee Tan, Hong-Jian Zhu, Sam Wormald, Antony W Burgess
Mathematical models for TGF-β and IL-6 signalling have been linked, providing a platform for analyzing the crosstalk between the systems. An integrated IL-6:TGF-β model was developed via a reduced set of reaction equations which incorporate both feedback loops and appropriate time-delays for transcription and translation processes. The model simulates stable, robust and realistic responses to both ligands. Pulsatile (multiple pulses) inputs for both TGF-β and IL-6 have been simulated to investigate the effects of each ligand on the sensitivity, equilibrium and dynamic responses of the integrated signalling system...
June 2017: Growth Factors
https://www.readbyqxmd.com/read/28883791/proteasome-inhibitor-ysy01a-abrogates-constitutive-stat3-signaling-via-down-regulation-of-gp130-and-jak2-in-human-a549-lung-cancer-cells
#19
Wei Huang, Xia Yuan, Ting Sun, Shujie Fan, Jun Wang, Quan Zhou, Wei Guo, Fuxiang Ran, Zemei Ge, Huayu Yang, Runtao Li, Jingrong Cui
Proteasome inhibition interfering with many cell signaling pathways has been extensively explored as a therapeutic strategy for cancers. Proteasome inhibitor YSY01A is a novel agent that has shown remarkable anti-tumor effects; however, its mechanisms of action are not fully understood. Here we report that YSY01A is capable of suppressing cancer cell survival by induction of apoptosis. Paradoxically, we find that YSY01A abrogates constitutive activation of STAT3 via proteasome-independent degradation of gp130 and JAK2, but not transcriptional regulation, in human A549 non-small cell lung cancer cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28882904/frontline-science-proliferation-of-ly6c-monocytes-during-urinary-tract-infections-is-regulated-by-il-6-trans-signaling
#20
Akanksha Dixit, Jenny Bottek, Anna-Lena Beerlage, Jana Schuettpelz, Stephanie Thiebes, Alexandra Brenzel, Christoph Garbers, Stefan Rose-John, Hans-Willi Mittrücker, Anthony Squire, Daniel R Engel
Ly6C(+) monocytes are important components of the innate immune defense against infections. These cells have been shown to proliferate in the bone marrow of mice with systemic infections. However, the proliferative capacity of Ly6C(+) monocytes in infected peripheral tissues as well as the associated regulatory mechanisms remain unclear. In this study, we analyzed the proliferative capacity of Ly6C(+) monocytes in the urinary bladder after infection with uropathogenic E. coli, one of the most prevalent pathogen worldwide, and in LPS-induced peritonitis...
September 7, 2017: Journal of Leukocyte Biology
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