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https://www.readbyqxmd.com/read/28442624/unphosphorylated-isgf3-drives-constitutive-expression-of-interferon-stimulated-genes-to-protect-against-viral-infections
#1
Wenshi Wang, Yuebang Yin, Lei Xu, Junhong Su, Fen Huang, Yijin Wang, Patrick P C Boor, Kan Chen, Wenhui Wang, Wanlu Cao, Xinying Zhou, Pengyu Liu, Luc J W van der Laan, Jaap Kwekkeboom, Maikel P Peppelenbosch, Qiuwei Pan
Interferon (IFN)-stimulated genes (ISGs) are antiviral effectors that are induced by IFNs through the formation of a tripartite transcription factor ISGF3, which is composed of IRF9 and phosphorylated forms of STAT1 and STAT2. However, we found that IFN-independent ISG expression was detectable in immortalized cell lines, primary intestinal and liver organoids, and liver tissues. The constitutive expression of ISGs was mediated by the unphosphorylated ISGF3 (U-ISGF3) complex, consisting of IRF9 together with unphosphorylated STAT1 and STAT2...
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28440408/identification-of-potential-gene-targets-in-systemic-vasculitis-using-dna-microarray-analysis
#2
Yiwen Feng, Miao Zheng, Shujie Gan, Lei Zhang, Zhong Wan, Yanping Zhang, Qin Qian, Jingdong Tang
The present study aimed to identify the involvement of critical genes in systemic vasculitis, to gain an improved understanding of the molecular circuity and to investigate novel potential gene targets for systemic vasculitis treatment. The dual‑color cDNA microarray data of GSE16945, consisting of peripheral mononuclear blood cell specimens from 13 patients with systemic vasculitis and 16 healthy controls, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened in systemic vasculitis compared with controls using BRB ArrayTools, followed by the construction of a protein‑protein interaction (PPI) network using the clusterProfiler package, and significant functional interaction (FI) module selection...
April 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440396/downregulation-of-mir-10b-promotes-osteoblast-differentiation-through-targeting-bcl6
#3
Jizhou Yang, Shaojie Wang, Fengxian Wang, Xiaohong Mu, Yi Qu, Ziyi Zhao, Xing Yu
MicroRNAs (miRNAs or miRs) have been shown to play a critical role in osteoblast differentiation. miR-10b has been found to be downregulated during osteoblast differentiation; however, its precise effect on osteoblast differentiation remains unknown. In this study, we aimed to investigate the potential role of miR-10b and the potential underlying mechanism in regulating osteoblast differentiation. We found that miR-10b was downregulated during osteoblast differentiation. Overexpression of miR-10b inhibited osteoblast differentiation, whereas the suppression of miR-10b promoted osteoblast differentiation...
April 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28438776/the-immunoproteasome-is-induced-by-cytokines-and-regulates-apoptosis-in-human-islets
#4
Morten Lundh, Marco Bugliani, Tina Dahlby, Danny Hung-Chieh Chou, Bridget Wagner, Seyed Mojtaba Ghiasi, Vincenzo De Tata, Zhifei Chen, Marianne Nissen Lund, Michael J Davies, Piero Marchetti, Thomas Mandrup-Poulsen
In addition to degrading misfolded and damaged proteins, the proteasome regulates the fate of cells in response to stress. The role of the proteasome in pro-inflammatory cytokine-induced human beta-cell apoptosis is unknown. INS-1, INS-1E and human islets were exposed to combinations of IFNγ, IL-1β and TNFα with or without addition of small molecules. Gene expression was assessed by microarray or quantitative PCR. Proteasome activities were analyzed using luminescent assays. Protein oxidation, Western blotting and electron microscopy were used to examine mechanisms underlying cytokine-induced apoptosis...
April 24, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28438564/essential-oil-of-artemisia-argyi-suppresses-inflammatory-responses-by-inhibiting-jak-stats-activation
#5
Lin-Lin Chen, Hao-Jun Zhang, Jung Chao, Jun-Feng Liu
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi is a herbal medicine traditionally used in Asia for the treatment of bronchitis, dermatitis and arthritis. Recent studies revealed the anti-inflammatory effect of essential oil in this plant. However, the mechanisms underlying the therapeutic potential have not been well elucidated. The present study is aimed to verify anti-inflammatory effect and investigate the probable mechanisms. MATERIALS AND METHODS: The essential oil from Artemisia argyi (AAEO) was initially tested against LPS-induced production of inflammatory mediators and cytokines in RAW264...
April 21, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28432285/nod1-modulates-il-10-signalling-in-human-dendritic-cells
#6
Theresa Neuper, Kornelia Ellwanger, Harald Schwarz, Thomas A Kufer, Albert Duschl, Jutta Horejs-Hoeck
NOD1 belongs to the family of NOD-like receptors, which is a group of well-characterised, cytosolic pattern-recognition receptors. The best-studied function of NOD-like receptors is their role in generating immediate pro-inflammatory and antimicrobial responses by detecting specific bacterial peptidoglycans or by responding to cellular stress and danger-associated molecules. The present study describes a regulatory, peptidoglycan-independent function of NOD1 in anti-inflammatory immune responses. We report that, in human dendritic cells, NOD1 balances IL-10-induced STAT1 and STAT3 activation by a SOCS2-dependent mechanism, thereby suppressing the tolerogenic dendritic cell phenotype...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432122/dual-regulation-of-stat1-and-stat3-by-the-tumor-suppressor-protein-pml-contributes-to-ifn%C3%AE-mediated-inhibition-of-angiogenesis
#7
Kuo-Sheng Hsu, Xuan Zhao, Xiwen Cheng, Dongyin Guan, Ganapati H Mahabeleshwar, Yu Liu, Ernest Borden, Mukesh K Jain, Hung-Ying Kao
IFNs are effective in inhibiting angiogenesis in preclinical models and in treating several angio-proliferative disorders. However, the detailed mechanisms of IFNα-mediated anti-angiogenesis are not completely understood. Stat1/2/3 and PML are IFNα downstream effectors and are pivotal regulators of angiogenesis. Here, we investigated PML's role in the regulation of Stat1/2/3 activity. In Pml knockout (KO) mice, ablation of Pml largely reduces IFNα angiostatic ability in Matrixgel plug assays. This suggested an essential role for PML in IFNα's anti-angiogenic function...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28431406/erk-expression-and-its-correlation-with-stat1-in-esophageal-squamous-cell-carcinoma
#8
Hu Wang, Ying Zhang, Hailong Yun, Shubiao Chen, Yelong Chen, Zhaoyong Liu
BACKGROUND: Esophageal squamous cell carcinoma is one of leading causes of cancer-related deaths in Chaoshan region a high-risk region for esophageal cancer. Extracellular regulated protein kinases (ERK) usually play an important role in cell proliferation and differentiation. However, accumulating evidence has shown that the ERK was aberrantly expressed in cancers and correlated with STAT1 depression. RESULTS: The activated ERK downregulates STAT1 expression in ESCC cell lines and U0126 increases expression of STAT1...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#9
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/28428136/hesperetin-derivative-14-alleviates-inflammation-by-activating-ppar-%C3%AE-in-mice-with-ccl4-induced-acute-liver-injury-and-lps-treated-raw264-7-cells
#10
Xin Chen, Hai-Wen Ding, Hai-Di Li, Hui-Min Huang, Xiao-Feng Li, Yang Yang, Yi-Long Zhang, Xue-Yin Pan, Cheng Huang, Xiao-Ming Meng, Jun Li
Hesperetin is a flavanone glycoside compound naturally occurring in the fruit peel of Citrusaurantium L. (Rutaceae). Previous studies revealed that hesperetin possesses various pharmacological effects, including anti-inflammation, anti-tumor, anti-oxidant and neuroprotective properties. Hesperetin derivative-14 (HD-14) is a derivative of hesperetin improved in water solubility and bioavailability. In this study, we indicated that HD-14 (2μM) significantly attenuated inflammation in LPS-treated RAW264.7 cells and had hepato-protective effects and anti-inflammatory effects (100mg/kg) on C57BL/6J mice with CCl4-induced acute liver injury...
April 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28427548/autosomal-dominant-gain-of-function-stat1-mutation-and-severe-bronchiectasis
#11
Oded Breuer, Hagit Daum, Malena Cohen-Cymberknoh, Susanne Unger, David Shoseyov, Polina Stepensky, Baerbel Keller, Klaus Warnatz, Eitan Kerem
BACKGROUND: In a substantial number of patients with non-cystic fibrosis (CF) bronchiectasis an etiology cannot be found. Various complex immunodeficiency syndromes account for a significant portion of these patients but the mechanism elucidating the predisposition for suppurative lung disease often remains unknown. OBJECTIVE: To investigate the cause and mechanism predisposing a patient to severe bronchiectasis. METHODS: A patient presenting with severe non-CF bronchiectasis was investigated...
May 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28427244/whole-genome-expression-analyses-of-type-2-diabetes-in-human-skin-reveal-altered-immune-function-and-burden-of-infection
#12
Chun Wu, Xiaopan Chen, Jing Shu, Chun-Ting Lee
Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426911/tbk1-ikke-blockade-inhibits-mutant-sting-mediated-inflammatory-response-in-patient-cells
#13
Marie-Louise Frémond, Carolina Uggenti, Lien Van Eyck, Isabelle Melki, Vincent Bondet, Naoki Kitabayashi, Christina Hertel, Adrian Hayday, Bénédicte Neven, Yoann Rose, Darragh Duffy, Yanick J Crow, Mathieu P Rodero
OBJECTIVE: Gain-of-function mutations in TMEM173 encoding STING (stimulator of interferon genes) underlie a novel type I interferonopathy, minimally responsive to conventional immunosuppressive therapies and associated with high childhood morbidity and mortality. STING gain-of-function causes constitutive over secretion of interferon (IFN). We determined the effects of a TBK1/IKKE inhibitor (BX795) on IFN secretion and signaling in primary peripheral blood mononuclear cells (PBMCs) from four patients...
April 20, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28425483/a-genome-wide-association-study-identifies-six-novel-risk-loci-for-primary-biliary-cholangitis
#14
Fang Qiu, Ruqi Tang, Xianbo Zuo, Xingjuan Shi, Yiran Wei, Xiaodong Zheng, Yaping Dai, Yuhua Gong, Lan Wang, Ping Xu, Xiang Zhu, Jian Wu, Chongxu Han, Yueqiu Gao, Kui Zhang, Yuzhang Jiang, Jianbo Zhou, Youlin Shao, Zhigang Hu, Ye Tian, Haiyan Zhang, Na Dai, Lei Liu, Xudong Wu, Weifeng Zhao, Xiaomin Zhang, Zhidong Zang, Jinshan Nie, Weihao Sun, Yi Zhao, Yuan Mao, Po Jiang, Hualiang Ji, Qing Dong, Junming Li, Zhenzhong Li, Xinli Bai, Li Li, Maosong Lin, Ming Dong, Jinxin Li, Ping Zhu, Chan Wang, Yanqiu Zhang, Peng Jiang, Yujue Wang, Rohil Jawed, Jing Xu, Yu Zhang, Qixia Wang, Yue Yang, Fan Yang, Min Lian, Xiang Jiang, Xiao Xiao, Yanmei Li, Jingyuan Fang, Dekai Qiu, Zhen Zhu, Hong Qiu, Jianqiong Zhang, Wenyan Tian, Sufang Chen, Ling Jiang, Bing Ji, Ping Li, Guochang Chen, Tianxue Wu, Yan Sun, Jianjiang Yu, Huijun Tang, Michun He, Min Xia, Hao Pei, Lihua Huang, Zhuye Qing, Jianfang Wu, Qinghai Huang, Junhai Han, Wei Xie, Zhongsheng Sun, Jian Guo, Gengsheng He, M Eric Gershwin, Zhexiong Lian, Xiang Liu, Michael F Seldin, Xiangdong Liu, Weichang Chen, Xiong Ma
Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3 (STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-κB) and 22q13...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28425456/salt-suppresses-ifn%C3%AE-inducible-chemokines-through-the-ifn%C3%AE-jak1-stat1-signaling-pathway-in-proximal-tubular-cells
#15
Yohei Arai, Daiei Takahashi, Kenichi Asano, Masato Tanaka, Mayumi Oda, Shigeru B H Ko, Minoru S H Ko, Shintaro Mandai, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
The mechanisms of immunoactivation by salt are now becoming clearer. However, those of immunosuppression remain unknown. Since clinical evidence indicates that salt protects proximal tubules from injury, we investigated mechanisms responsible for salt causing immunosuppression in proximal tubules. We focused on cytokine-related gene expression profiles in kidneys of mice fed a high salt diet using microarray analysis and found that both an interferon gamma (IFNγ) inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor, CXCR3, were suppressed...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424277/janus-kinase-2-regulates-transcription-factor-eb-expression-and-autophagy-completion-in-glomerular-podocytes
#16
Tamadher A Alghamdi, Syamantak Majumder, Karina Thieme, Sri N Batchu, Kathryn E White, Youan Liu, Angela S Brijmohan, Bridgit B Bowskill, Suzanne L Advani, Minna Woo, Andrew Advani
The nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a promising therapeutic target for the treatment of CKD. However, being ubiquitously expressed in the adult, JAK2 is also likely to be necessary for normal organ function. Here, we investigated the phenotypic effects of JAK2 deficiency. Mice in which JAK2 had been deleted from podocytes exhibited an elevation in urine albumin excretion that was accompanied by increased podocyte autophagosome fractional volume and p62 aggregation, which are indicative of impaired autophagy completion...
April 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28422733/the-transcriptional-stat3-is-a-potential-target-whereas-transcriptional-stat5a-5b-6-are-new-biomarkers-for-prognosis-in-human-breast-carcinoma
#17
Hua-Tao Wu, Jing Liu, Guan-Wu Li, Jia-Xin Shen, Yi-Teng Huang
Signal Transducer and Activators of Transcription (STAT) is a set of transcription factors, involved in diverse cellular functions. Evidences from cell lines, mouse models and human tissues implicate these transcription factors in the oncogenesis of breast cancer. However, the diverse expression patterns and prognostic values of 7 STATs remain to be elucidated. In the current study, we mined the transcriptional and survival data of STATs in patients with breast carcinoma (BC) through ONCOMINE, bc-GenExMiner, Kaplan-Meier Plotter and cBioPortal...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422713/sel120-34a-is-a-novel-cdk8-inhibitor-active-in-aml-cells-with-high-levels-of-serine-phosphorylation-of-stat1-and-stat5-transactivation-domains
#18
Tomasz Rzymski, Michał Mikula, Eliza Żyłkiewicz, Agnieszka Dreas, Katarzyna Wiklik, Aniela Gołas, Katarzyna Wójcik, Magdalena Masiejczyk, Anna Wróbel, Izabela Dolata, Agata Kitlińska, Małgorzata Statkiewicz, Urszula Kuklinska, Krzysztof Goryca, Łukasz Sapała, Aleksandra Grochowska, Aleksandra Cabaj, Małgorzata Szajewska-Skuta, Ewelina Gabor-Worwa, Katarzyna Kucwaj, Arkadiusz Białas, Adam Radzimierski, Michał Combik, Jakub Woyciechowski, Maciej Mikulski, Renata Windak, Jerzy Ostrowski, Krzysztof Brzózka
Inhibition of oncogenic transcriptional programs is a promising therapeutic strategy. A substituted tricyclic benzimidazole, SEL120-34A, is a novel inhibitor of Cyclin-dependent kinase 8 (CDK8), which regulates transcription by associating with the Mediator complex. X-ray crystallography has shown SEL120-34A to be a type I inhibitor forming halogen bonds with the protein's hinge region and hydrophobic complementarities within its front pocket. SEL120-34A inhibits phosphorylation of STAT1 S727 and STAT5 S726 in cancer cells in vitro...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421993/increased-expression-of-interferon-%C3%AE-in-minor-salivary-glands-of-patients-with-primary-sj%C3%A3-gren-s-syndrome-and-its-synergic-effect-with-interferon-%C3%AE-on-salivary-gland-epithelial-cells
#19
You-Jung Ha, Yong Seok Choi, Eun Ha Kang, Jin-Haeng Chung, Seunghee Cha, Yeong Wook Song, Yun Jong Lee
OBJECTIVES: To investigate the expressions of interferon (IFN)-λs and their receptor, IL28RA, in minor salivary glands (MSG) of pSS patients and their effects on the salivary gland cells. METHODS: The expressions of IFN-λs and IL28RA were evaluated in MSG by immunohistochemistry in 15 patients with pSS and in 5 patients with non-SS sicca. Poly(I:C)-induced IL-28A and IL-29 expressions were determined in immortalized human salivary gland acinar (NS-SV-AC) and ductal (NS-SV-DC) cell lines...
April 18, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28418858/the-mir-124-p63-feedback-loop-modulates-colorectal-cancer-growth
#20
Kuijie Liu, Hongliang Yao, Sanlin Lei, Li Xiong, Haizhi Qi, Ke Qian, Jiqiang Liu, Peng Wang, Hua Zhao
Among the diverse co-regulatory relationships between transcription factors (TFs) and microRNAs (miRNAs), feedback loops have received the most extensive research attention. The co-regulation of TFs and miRNAs plays an important role in colorectal cancer (CRC) growth. Here, we show that miR-124 can regulate two isoforms of p63, TAp63 and ΔNp63, via iASPP, while p63 modulates signal transducers and activators of transcription 1 (STAT1) expression by targeting miR-155. Moreover, STAT1 acts as a regulator of CRC growth by targeting miR-124...
March 16, 2017: Oncotarget
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