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Margarita Arango-Lievano, Camille Peguet, Matthias Catteau, Marie-Laure Parmentier, Synphen Wu, Moses V Chao, Stephen D Ginsberg, Freddy Jeanneteau
Glucocorticoid resistance is a risk factor for Alzheimer's disease (AD). Molecular and cellular mechanisms of glucocorticoid resistance in the brain have remained unknown and are potential therapeutic targets. Phosphorylation of glucocorticoid receptors (GR) by brain-derived neurotrophic factor (BDNF) signaling integrates both pathways for remodeling synaptic structure and plasticity. The goal of this study is to test the role of the BDNF-dependent pathway on glucocorticoid signaling in a mouse model of glucocorticoid resistance...
November 16, 2016: Scientific Reports
Victoria A McGuire, Dalya Rosner, Olga Ananieva, Ewan A Ross, Suzanne E Elcombe, Shaista Naqvi, Mirjam M W van den Bosch, Claire E Monk, Tamara Ruiz-Zorrilla Diez, Andrew R Clark, J Simon C Arthur
Autocrine or paracrine signaling by the type I interferon IFNβ is essential for many of the responses of macrophages to pathogen-associated molecular patterns. This feedback loop contributes to pathological responses to infectious agents, and is therefore tightly regulated. We demonstrate here that macrophage expression of IFNβ is negatively regulated by mitogen- and stress-activated kinases (MSK) 1 and 2. Lipopolysaccharide- (LPS-) induced expression of IFNβ was elevated in both MSK1/2 knockout mice and macrophages...
October 17, 2016: Molecular and Cellular Biology
R X Hou, R F Liu, X C Zhao, Y R Jia, P An, Z P Hao, J Q Li, X H Li, G H Yin, K M Zhang
Mesenchymal stem cells (MSCs) have pleiotropic immuno-modulatory effects and pro-angiogenic ability, leading to the presumption that MSCs may be involved in the pathogenesis of many inflammatory or autoimmune disorders, including psoriasis. In a previous study, we reported the specific gene expression profile of dermal MSCs from psoriasis. Inflammation- and angiogenesis-related genes, such as lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor (LITAF), dual-specificity protein phosphatase 1 (DUSP1), vascular endothelial growth factor α (VEGFα), and insulin-like growth factor-binding protein-5 (IGFBP5), are abnormally expressed in psoriatic dermal MSCs...
September 2, 2016: Genetics and Molecular Research: GMR
Neha Kapila, Ankita Sharma, Amit Kishore, Monika Sodhi, Pawan K Tripathi, Ashok K Mohanty, Manishi Mukesh
The present study aims to identify the heat responsive genes and biological pathways in heat stressed buffalo mammary epithelial cells (MECs). The primary mammary epithelial cells of riverine buffalo were exposed to thermal stress at 42°C for one hour. The cells were subsequently allowed to recover at 37°C and harvested at different time intervals (30 min to 48 h) along with control samples (un-stressed). In order to assess the impact of heat stress in buffalo MECs, several in-vitro cellular parameters (lactate dehydrogenase activity, cell proliferation assay, cellular viability, cell death and apoptosis) and transcriptional studies were conducted...
2016: PloS One
Robert Newton, Mark A Giembycz
In moderate-to-severe asthma, adding an inhaled long-acting β2 -adenoceptor agonist (LABA) to an inhaled corticosteroid (ICS) provides better disease control than simply increasing the dose of ICS. Acting on the glucocorticoid receptor (GR, gene NR3C1), ICSs promote anti-inflammatory/anti-asthma gene expression. In vitro, LABAs synergistically enhance the maximal expression of many glucocorticoid-induced genes. Other genes, including dual-specificity phosphatase 1(DUSP1) in human airways smooth muscle (ASM) and epithelial cells, are up-regulated additively by both drug classes...
December 2016: British Journal of Pharmacology
Daniel Nettersheim, Sina Jostes, Martin Fabry, Friedemann Honecker, Valerie Schumacher, Jutta Kirfel, Glen Kristiansen, Hubert Schorle
In Western countries, the incidence of testicular germ cell cancers (GCC) is steadily rising over the last decades. Mostly, men between 20 and 40 years of age are affected. In general, patients suffering from GCCs are treated by orchiectomy and radio- or chemotherapy. Due to resistance mechanisms, intolerance to the therapy or denial of chemo- / radiotherapy by the patients, GCCs are still a lethal threat, highlighting the need for alternative treatment strategies.In this study, we revealed that germ cell cancer cell lines are highly sensitive to the histone deacetylase inhibitor romidepsin in vitro and in vivo, highlighting romidepsin as a potential therapeutic option for GCC patients...
August 27, 2016: Oncotarget
Suharsh Shah, Elizabeth M King, Mahmoud M Mostafa, Mohammed O Altonsy, Robert Newton
Although the mitogen-activated protein kinase (MAPK) phosphatase, DUSP1, mediates dexamethasone-induced repression of MAPKs, 14 of 46 interleukin-1β (IL1B)-induced mRNAs were significantly enhanced by DUSP1 overexpression in pulmonary A549 cells. These include the interferon regulatory factor, IRF1, and the chemokine, CXCL10. Of these, DUSP1-enhanced mRNAs, 10 including CXCL10, were IRF1-dependent. MAPK inhibitors and DUSP1 overexpression prolonged IRF1 expression by elevating transcription and increasing IRF1 mRNA and protein stability...
October 7, 2016: Journal of Biological Chemistry
Juan Wang, Jun-Ying Zhou, Dhonghyo Kho, John J Reiners, Gen Sheng Wu
Accumulating evidence suggests that mitogen-activated protein kinases (MAPKs) regulate macroautophagy/autophagy. However, the involvement of dual-specificity protein phosphatases (DUSPs), endogenous inhibitors for MAPKs, in autophagy remains to be determined. Here we report that DUSP1/MKP-1, the founding member of the DUSP family, plays a critical role in regulating autophagy. Specifically, we demonstrate that DUSP1 knockdown by shRNA in human ovarian cancer CAOV3 cells and knockout in murine embryonic fibroblasts, increases both basal and rapamycin-increased autophagic flux...
October 2, 2016: Autophagy
Jin Young Lee, Kyung-Rok Yu, Hyung-Sik Kim, Insung Kang, Jae-Jun Kim, Byung-Chul Lee, Soon Won Choi, Ji-Hee Shin, Yoojin Seo, Kyung-Sun Kang
For the application of mesenchymal stem cells (MSCs) as clinical therapeutics, the regulation of cellular aging is important to protect hMSCs from an age-associated decline in their function. In this study, we evaluated the effects of hypoxia on cellular senescence and the immunomodulatory abilities of hUCB-MSCs. Hypoxic-cultured hUCB-MSCs showed enhanced proliferation and had increased immunosuppressive effects on mitogen-induced mononuclear cell proliferation. We found that BMI1, a member of the polycomb repressive complex protein group, showed increased expression in hypoxic-cultured hUCB-MSCs, and the further knock-down of BMI1 in hypoxic cells induced decreased proliferative and immunomodulatory abilities in hUCB-MSCs, along with COX-2/PGE2 down-regulation...
August 2016: Aging
Jun Shi, Ying Zhang, Shanshan Qi, Guanghui Liu, Xiang Dong, Nan Huang, Wenjing Li, Hao Chen, Bingmei Zhu
The aim of this study was to reveal a potential key gene network associated with seasonal allergic rhinitis (SAR). The microarray data GSE50101 downloaded from Gene Expression Omnibus were used to screen differentially expressed genes (DEGs) between SAR patients and healthy controls. Then, functional enrichment analysis was conducted using Database for Annotation, Visualization, and Integrated Discovery. Afterwards, the protein-protein interactions (PPIs) of DEGs were obtained from STRING, and the PPI network was constructed...
July 19, 2016: European Archives of Oto-rhino-laryngology
Yu-Seon Kang, Hyun-Jeong Seok, Eun-Jeong Jeong, Yuna Kim, Seok-Joong Yun, Jeong-Ki Min, Sun Jin Kim, Jang-Seong Kim
The heterogeneity and genetic instability of ovarian cancer cells often lead to the development of drug resistance, closely related with the increased cancer-related mortality. In this study, we investigated the role of dual-specificity phosphatase 1 (DUSP1) in the development of the resistance in human ovarian cancer cells against paclitaxel. Overexpression of DUSP1 in HeyA8 human ovarian cancer cells (HeyA8-DUSP1) up-regulated the expression of the drug efflux pump, p-glycoprotein. Consequently, HeyA8-DUSP1 cells are highly resistant to paclitaxel, with the resistance comparable to that of a multi-drug resistance cell line (HeyA8-MDR)...
September 9, 2016: Biochemical and Biophysical Research Communications
Demet Candas, Jian Jian Li
Mitogen-activated protein kinase phosphatase 1 (MKP1 or DUSP1) is an antiapoptotic phosphatase that is overexpressed in many cancers, including breast cancer. MKP1 expression is inducible in radiation-treated breast cancer cells, and correlates with human epidermal growth factor receptor 2 (ERBB2, HER2) expression. The role of MKP1 in therapy resistance suggests that targeting MKP1 in HER2-positive breast tumors may significantly enhance the efficacy of anti-HER2 and other anticancer therapies.
October 2015: Molecular & Cellular Oncology
Jiliang Shen, Yaping Zhang, Hong Yu, Bo Shen, Yuelong Liang, Renan Jin, Xiaolong Liu, Liang Shi, Xiujun Cai
Dual-specificity phosphatase-1 (DUSP1/MKP1), as a member of the threonine-tyrosine dual-specificity phosphatase family, was first found in cultured murine cells. The molecular mechanisms of DUSP1-mediated extracellular signal-regulated protein kinases (ERKs) dephosphorylation have been subsequently identified by studies using gene knockout mice and gene silencing technology. As a protein phosphatase, DUSP1 also downregulates p38 MAPKs and JNKs signaling through directly dephosphorylating threonine and tyrosine...
August 2016: Cancer Medicine
Christopher Tiedje, Manuel D Diaz-Muñoz, Philipp Trulley, Helena Ahlfors, Kathrin Laaß, Perry J Blackshear, Martin Turner, Matthias Gaestel
RNA-binding proteins (RBPs) facilitate post-transcriptional control of eukaryotic gene expression at multiple levels. The RBP tristetraprolin (TTP/Zfp36) is a signal-induced phosphorylated anti-inflammatory protein guiding unstable mRNAs of pro-inflammatory proteins for degradation and preventing translation. Using iCLIP, we have identified numerous mRNA targets bound by wild-type TTP and by a non-MK2-phosphorylatable TTP mutant (TTP-AA) in 1 h LPS-stimulated macrophages and correlated their interaction with TTP to changes at the level of mRNA abundance and translation in a transcriptome-wide manner...
September 6, 2016: Nucleic Acids Research
Joanna Ficek, Magdalena Zygmunt, Marcin Piechota, Dzesika Hoinkis, Jan Rodriguez Parkitna, Ryszard Przewlocki, Michal Korostynski
BACKGROUND: The NMDA receptor antagonist ketamine was found to act as a fast-acting antidepressant. The effects of single treatment were reported to persist for days to weeks, even in otherwise treatment-refractory cases. Identification of the mechanisms underlying ketamine's antidepressant action may permit development of novel drugs, with similar clinical properties but lacking psychotomimetic, sedative and other side effects. METHODS: We applied whole-genome microarray profiling to analyze detailed time-course (1, 2, 4 and 8 h) of transcriptome alterations in the striatum and hippocampus following acute administration of ketamine, memantine and phencyclidine in C57BL/6 J mice...
2016: BMC Genomics
Yuan Yang, Jing-Yi Zhou, Li-Jun Zhao, Bao-Rong Gao, Xiao-Ping Wan, Jian-Liu Wang
BACKGROUND: Previously, we reported that dual-specificity phosphatase 1 (DUSP1) was differentially expressed in endometrioid adenocarcinoma (EEA). However, the role of DUSP1 in EEA progression and the relationship between DUSP1 and medroxyprogesterone (MPA) are still unclear. METHODS: The expression of DUSP1 in EEA specimens was detected by immunohistochemical analysis. The effect of DUSP1 on cell proliferation was analyzed by Cell Counting Kit 8 and colony formation assay, and cell migration was analyzed by transwell assay...
May 20, 2016: Chinese Medical Journal
Heng Boon Low, Yongliang Zhang
The mitogen-activated protein kinases (MAPKs) are key regulators of cell growth and survival in physiological and pathological processes. Aberrant MAPK signaling plays a critical role in the development and progression of human cancer, as well as in determining responses to cancer treatment. The MAPK phosphatases (MKPs), also known as dual-specificity phosphatases (DUSPs), are a family of proteins that function as major negative regulators of MAPK activities in mammalian cells. Studies using mice deficient in specific MKPs including MKP1/DUSP1, PAC-1/DUSP2, MKP2/DUSP4, MKP5/DUSP10 and MKP7/DUSP16 demonstrated that these molecules are important not only for both innate and adaptive immune responses, but also for metabolic homeostasis...
April 2016: Immune Network
Karim Malki, Ebba Du Rietz, Wim E Crusio, Oliver Pain, Jose Paya-Cano, Rezhaw L Karadaghi, Frans Sluyter, Sietse F de Boer, Kenneth Sandnabba, Leonard C Schalkwyk, Philip Asherson, Maria Grazia Tosto
Despite moderate heritability estimates, the molecular architecture of aggressive behavior remains poorly characterized. This study compared gene expression profiles from a genetic mouse model of aggression with zebrafish, an animal model traditionally used to study aggression. A meta-analytic, cross-species approach was used to identify genomic variants associated with aggressive behavior. The Rankprod algorithm was used to evaluated mRNA differences from prefrontal cortex tissues of three sets of mouse lines (N = 18) selectively bred for low and high aggressive behavior (SAL/LAL, TA/TNA, and NC900/NC100)...
September 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Krisztina Köröskényi, Beáta Kiss, Zsuzsa Szondy
Adenosine is known to reduce inflammation by suppressing the activity of most immune cells. Previous studies have shown that lipopolysaccharide (LPS) stimulated mouse macrophages produce adenosine, and the adenosine A2A receptor (A2AR) signaling activated in an autocrine manner attenuates LPS-induced pro-inflammatory cytokine formation. It has been suggested that A2AR signaling inhibits LPS-induced pro-inflammatory cytokine production through a unique cAMP-dependent, but PKA- and Epac-independent signaling pathway...
July 2016: Biochimica et Biophysica Acta
Zu-Yau Lin, Chao-Hung Kuo, Deng-Chyang Wu, Wan-Long Chuang
Colchicine is a very cheap microtubule destabilizer. Because microtubules are an ideal target for anticancer drugs, the purpose of this study was to investigate whether clinically acceptable colchicine concentrations have anticancer effects on gastric cancer cells, and its possible anticancer mechanisms. Two human gastric cancer cell lines (i.e., AGS and NCI-N87) were investigated by proliferative assay, microarray, quantitative reverse transcriptase-polymerase chain reaction, and a nude mice study using clinically acceptable colchicine concentrations (2 ng/mL and 6 ng/mL for in vitro tests and 0...
February 2016: Kaohsiung Journal of Medical Sciences
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