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https://www.readbyqxmd.com/read/29038846/a-possible-implication-of-reduced-levels-of-lif-lifr-and-gp130-in-vasculopathy-related-to-systemic-sclerosis
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
September 29, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28948853/tgf-%C3%AE-and-il-6-family-signalling-crosstalk-an-integrated-model
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28881473/the-classic-signalling-and-trans-signalling-of-interleukin-6-are-both-injurious-in-podocyte-under-high-glucose-exposure
#11
Chun-Tao Lei, Hua Su, Chen Ye, Hui Tang, Pan Gao, Cheng Wan, Fang-Fang He, Yu-Mei Wang, Chun Zhang
Interleukin-6 (IL-6) is a multifunctional cytokine that employs IL-6 classic and trans-signalling pathways, and these two signal channels execute different or even opposite effects in certain diseases. As a cardinal event of diabetic kidney disease (DKD), whether the podocyte abnormalities are associated with IL-6 signalling, especially classic or trans-signalling respectively, remains unclear. In this study, we identified that the circulatory IL-6, soluble IL-6R (sIL-6R) and soluble glycoprotein 130 (sgp130) levels are elevated in patients with DKD...
September 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28879441/egfr-and-kras-mutations-do-not-enrich-for-the-activation-of-il-6-jak1-or-phosphorylated-stat3-in-resected-lung-adenocarcinoma
#12
Timothy D Clay, Prudence A Russell, Hongdo Do, Vijaya Sundararajan, Matthew Conron, Gavin M Wright, Benjamin Solomon, Alexander Dobrovic, Sue-Anne McLachlan, Melissa M Moore
Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) against EGFR mutant lung adenocarcinoma develops after a median of nine to thirteen months. Upregulation of the interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway may be a potential source of resistance to EGFR TKIs. We undertook a detailed assessment of the IL-6/JAK1/phosphorylated STAT3 (pSTAT3) pathway in resected lung adenocarcinoma specimens, with special interest in whether the presence of an EGFR mutation enriched for pSTAT3 positivity...
September 6, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28878084/human-herpesvirus-8-interleukin-6-interacts-with-calnexin-cycle-components-and-promotes-protein-folding
#13
Daming Chen, Qiwang Xiang, John Nicholas
Viral interleukin-6 (vIL-6) encoded by human herpesvirus 8 (HHV-8) is believed to contribute via mitogenic, survival, and angiogenic activities to HHV-8-associated Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease through autocrine or paracrine mechanisms during latency or productive replication. There is direct evidence that vIL-6 promotes latently infected PEL cell viability and proliferation and also viral productive replication in PEL and endothelial cells. These activities are mediated largely through endoplasmic reticulum (ER)-localized vIL-6, which can induce signal transduction via the gp130 signaling receptor, activating mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) signaling, and interactions of vIL-6 with the ER membrane protein vitamin K epoxide reductase complex subunit 1 variant 2 (VKORC1v2)...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28874583/smad7-enables-stat3-activation-and-promotes-pluripotency-independent-of-tgf-%C3%AE-signaling
#14
Yi Yu, Shuchen Gu, Wenjian Li, Chuang Sun, Fenfang Chen, Mu Xiao, Lei Wang, Dewei Xu, Ye Li, Chen Ding, Zongping Xia, Yi Li, Sheng Ye, Pinglong Xu, Bin Zhao, Jun Qin, Ye-Guang Chen, Xia Lin, Xin-Hua Feng
Smad7 is a negative feedback product of TGF-β superfamily signaling and fine tunes a plethora of pleiotropic responses induced by TGF-β ligands. However, its noncanonical functions independent of TGF-β signaling remain to be elucidated. Here, we show that Smad7 activates signal transducers and activators of transcription 3 (STAT3) signaling in maintaining mouse embryonic stem cell pluripotency in a manner independent of the TGF-β receptors, yet dependent on the leukemia inhibitory factor (LIF) coreceptor glycoprotein 130 (gp130)...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28874440/blocking-gp130-signaling-suppresses-autotaxin-expression-in-adipocytes-and-improves-insulin-sensitivity-in-diet-induced-obesity
#15
Shuhong Sun, Ran Wang, Jianwen Song, Ming Guan, Na Li, Xiaotian Zhang, Zhenwen Zhao, Junjie Zhang
Autotaxin (ATX), which is highly expressed and secreted by adipocytes, functions as the key enzyme to generate lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Adipose tissue is the main source of circulating ATX that modulates plasma LPA levels. Up-regulation of ATX expression in obese patients and mice is closely related with insulin resistance and impaired glucose tolerance. However, the mechanism of ATX expression in adipocytes remains largely unknown. In this study, we found that gp130-mediated JAK-STAT3 activation was required for abundant ATX expression in adipocytes...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28861079/tocilizumab-contributes-to-the-inflammatory-status-of-mature-dendritic-cells-through-interleukin-6-receptor-subunits-modulation
#16
Daniel Meley, Audrey Héraud, Valerie Gouilleux-Gruart, Fabrice Ivanes, Florence Velge-Roussel
Tocilizumab, a humanized anti-IL-6 receptor α (IL-6Rα) is widely used in the treatment of a panel of pathologies such as adult and juvenile rheumatoid arthritis (RA) and the systemic form of juvenile idiopathic arthritis in children. Its indications are expected to be largely extended to other inflammatory diseases in close future. Dendritic cells (DCs) appear to be deeply involved in the immunopathology of these diseases, yet the effects of tocilizumab on these cells were poorly studied. In this study, we explored the effect of tocilizumab on the regulation of IL-6R subunits [gp130, soluble form of IL-6Rα (sIL-6Rα), and mIL-6Rα] in human monocyte-derived DCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28827150/the-role-of-the-leukemia-inhibitory-factor-receptor-in-neuroprotective-signaling
#17
REVIEW
Stephanie M Davis, Keith R Pennypacker
Several neurotropic cytokines relay their signaling through the leukemia inhibitory factor receptor. This 190kDa subunit couples with the 130kDa gp130 subunit to transduce intracellular signaling in neurons and oligodendrocytes that leads to expression of genes associated with neurosurvival. Moreover, activation of this receptor alters the phenotype of immune cells to an anti-inflammatory one. Although cytokines that activate the leukemia inhibitory factor receptor have been studied in the context of neurodegenerative disease, therapeutic targeting of the specific receptor subunit has been understudied in by comparison...
August 18, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28820066/mutational-impact-on-the-interaction-between-human-il27-and-gp130-in-silico-approach-for-defending-hiv-infection
#18
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
#19
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
#20
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
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