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https://www.readbyqxmd.com/read/29682902/dusps-twists-and-turns-in-the-journey-to-vascular-inflammation
#1
Anton M Bennett
The MAPK phosphatase DUSP6/MKP-3 dephosphorylates ERK1 and 2 and negatively regulates ERK-dependent signaling. Hsu et al. now show that DUSP6/MKP-3 is required for the TNF-α-induced upregulation of the endothelial cell adhesion molecule-1 (ICAM-1) and neutrophil infiltration in endothelial cells, and interestingly, this positive role of DUSP6 on the inflammatory process is independent of ERK signaling.
April 22, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29661882/-in-vitro-antimicrobial-susceptibility-of-clinical-isolates-of-borrelia-miyamotoi
#2
Joris Koetsveld, Annemijn Manger, Dieuwertje Hoornstra, Ronald O Draga, Anneke Oei, Nadezhda M Kolyasnikova, Marina G Toporkova, Denis S Sarksyan, Alex Wagemakers, Alexander E Platonov, Joppe W Hovius
Objectives : Borrelia miyamotoi is an emerging relapsing fever (RF) Borrelia species that is described to cause human disease in regions where Lyme borreliosis is endemic. We have recently shown that B. miyamotoi tick isolates are resistant to amoxicillin in vitro, however, clinical isolates have not been studied. Therefore, our aim was to show antimicrobial susceptibility of recently obtained clinical isolates of B. miyamotoi Methods : A dilution series of various antibiotics was made in MKP-F media. Susceptibility of different clinical B...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29619028/mapk-phosphatase-1-deficiency-exacerbates-the-severity-of-imiquimod-induced-psoriasiform-skin-disease
#3
Weiheng Zhao, Shuxiu Xiao, Hongjin Li, Tingting Zheng, Jian Huang, Ran Hu, Baohua Zhang, Xinguang Liu, Gonghua Huang
Persistent activation of mitogen-activated protein kinase (MAPK) is believed to be involved in psoriasis pathogenesis. MAPK phosphatase-1 (MKP-1) is an important negative regulator of MAPK activity, but the cellular and molecular mechanisms of MKP-1 in psoriasis development are largely unknown. In this study, we found that the expression of MKP-1 was decreased in the imiquimod (IMQ)-induced psoriasiform mouse skin. MKP-1-deficient (MKP-1-/- ) mice were highly susceptible to IMQ-induced skin inflammation, which was associated with increased production of inflammatory cytokines and chemokines...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29580859/stage-iv-melanoma-of-unknown-primary-a-population-based-study-in-the-united-states-from-1973-to-2014
#4
Jeffrey F Scott, Ruzica Z Conic, Cheryl L Thompson, Meg R Gerstenblith, Jeremy S Bordeaux
BACKGROUND: Melanoma of unknown primary (MUP) is incompletely described on a population level. OBJECTIVE: We sought to characterize stage IV MUP in a population-based cancer registry. METHODS: We developed a novel search algorithm to identify cases of stage IV MUP in the Surveillance, Epidemiology, and End Results (SEER)-18 registries from 1973 to 2014. Stage IV melanoma of known primary (MKP) served as a comparison group. Age-standardized incidence rates, demographic characteristics, adjusted disease-specific survival (DSS), and Cox proportional hazard models were calculated for MUP and MKP...
March 23, 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29565504/mir-424-protects-pc-12-cells-from-ogd-induced-injury-by-negatively-regulating-mkp-1
#5
Y-X Cao, Z-Q Wang, J-X Kang, K Liu, C-F Zhao, Y-X Guo, B-H Jiao
OBJECTIVE: It's of great significance to investigate the novel targets of drugs for the treatment of stroke. In this study, we explored the neuroprotective role of miR-424 in oxygen glucose deprivation (OGD)-induced injuries in PC-12 cells. MATERIALS AND METHODS: PC-12 cells were subjected to OGD stimulation to mimic ischemic injury. The expressions of miR-424 and mitogen-activated protein kinase phosphatase-1 (MKP-1) were altered by transient transfection with miR-424 mimic, miR-424 inhibitor, pEX-MKP-1, or sh-MKP-1...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29501764/sinomenine-inhibits-lipopolysaccharide-induced-inflammatory-injury-by-regulation-of-mir-101-mkp-1-jnk-pathway-in-keratinocyte-cells
#6
Shumei Liu, Yigang Man, Li Zhao
OBJECTIVE: Recent studies have demonstrated that Sinomenine (SIN) exerted anti-inflammatory effect in various immune-related diseases. However, the effect of SIN on glucocorticoids dermatitis has not been investigated. In our study, we aimed to explore the effect of SIN on lipopolysaccharide (LPS)-induced inflammatory injury in HaCaT cells. MATERIALS AND METHODS: We constructed an inflammatory injury model of LPS-induced HaCaT cells, then SIN was added to LPS-treated cells, cell viability, apoptosis, apoptosis-associated factors and inflammatory cytokines were detected by CCK-8, flow cytometry, western blot, qRT-PCR and ELISA...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29494494/l-glutamine-attenuates-dss-induced-colitis-via-induction-of-mapk-phosphatase-1
#7
Soo-Yeon Jeong, Yoo Na Im, Ji Young Youm, Hern-Ku Lee, Suhn-Young Im
Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a multifactorial inflammatory disease of the small intestine and colon. Many investigators have reported that l-glutamine (Gln) therapy improves outcomes of experimental colitis models, although the mechanism is not fully understood. Regarding the anti-inflammatory properties of Gln, we have shown that Gln can effectively deactivate cytosolic phospholipase A₂ (cPLA₂) by rapid induction of MAPK phosphatase (MKP)-1. In this study, we explore the possibility that Gln ameliorates dextran sulfate sodium (DSS)-induced colitis via MKP-1 induction, resulting in inhibition of cPLA₂, which has been reported to play a key role in the pathogenesis of IBD...
March 1, 2018: Nutrients
https://www.readbyqxmd.com/read/29462804/angiotensin-ii-regulates-th1-t-cell-differentiation-through-angiotensin-ii-type-1-receptor-pka-mediated-activation-of-proteasome
#8
Xian-Yun Qin, Yun-Long Zhang, Ya-Fei Chi, Bo Yan, Xiang-Jun Zeng, Hui-Hua Li, Ying Liu
BACKGROUND/AIMS: Naive CD4+ T cells differentiate into T helper cells (Th1 and Th2) that play an essential role in the cardiovascular diseases. However, the molecular mechanism by which angiotensin II (Ang II) promotes Th1 differentiation remains unclear. The aim of this study was to determine whether the Ang II-induced Th1 differentiation regulated by ubiquitin-proteasome system (UPS). METHODS: Jurkat cells were treated with Ang II (100 nM) in the presence or absence of different inhibitors...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29455206/a-potential-mechanism-for-immune-suppression-by-beta-adrenergic-receptor-stimulation-following-traumatic-injury
#9
Nicholas J Shubin, Tam N Pham, Kristan Lea Staudenmayer, Brodie A Parent, Qian Qiu, Grant E O'Keefe
BACKGROUND: β-Adrenergic agents suppress inflammation and may play an important role in posttraumatic infections. Mechanisms may include inhibition of MAP kinase signaling. We sought to determine whether MKP-1 contributed to catecholamine suppression of innate immunity and also wanted to know whether early catecholamine treatment after traumatic injury increases the risk of later nosocomial infection. METHODS: We performed experiments using THP-1 cells and peripheral blood mononuclear cells from healthy individuals...
February 16, 2018: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29408518/a-chlorogenic-acid-phospholipid-complex-ameliorates-post-myocardial-infarction-inflammatory-response-mediated-by-mitochondrial-reactive-oxygen-species-in-samp8-mice
#10
Yi Li, Xuecong Ren, Chonkit Lio, Wenxia Sun, Ke Lai, Yuan Liu, Zhifeng Zhang, Jie Liang, Hua Zhou, Liang Liu, Hui Huang, Jing Ren, Pei Luo
Mitochondrial reactive oxygen species (mtROS) directly stimulate the inflammatory cytokines cascades and participate in age-related changes of cardiovascular diseases. Application of small molecule targeting the mtROS is significant towards development of better therapy to combat inflammatory response after myocardial infarction (MI) in the aging heart. Chlorogenic acid (CGA) is a well-known natural compound while the clinical potential is largely stifled by its poor oral absorption. In the present study, we tested the protective effect of a novel chlorogenic acid-phospholipid complex (CGA-PC) against acute post-MI inflammation in aged senescence accelerated mouse model...
April 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29317435/skeletal-muscle-specific-deletion-of-mkp-1-reveals-a-p38-mapk-jnk-akt-signaling-node-that-regulates-obesity-induced-insulin-resistance
#11
Ahmed Lawan, Kisuk Min, Lei Zhang, Alberto Canfran-Duque, Michael J Jurczak, Joao Paulo G Camporez, Yaohui Nie, Timothy P Gavin, Gerald I Shulman, Carlos Fernandez-Hernando, Anton M Bennett
Stress responses promote obesity and insulin resistance, in part, by activating the stress-responsive mitogen-activated protein kinases (MAPKs), p38 MAPK, and c-Jun NH2 -terminal kinase (JNK). Stress also induces expression of MAPK phosphatase-1 (MKP-1), which inactivates both JNK and p38 MAPK. However, the equilibrium between JNK/p38 MAPK and MKP-1 signaling in the development of obesity and insulin resistance is unclear. Skeletal muscle is a major tissue involved in energy expenditure and glucose metabolism...
April 2018: Diabetes
https://www.readbyqxmd.com/read/29241671/mkp-1-protects-mice-against-toxin-induced-liver-damage-by-promoting-the-nrf2-cytoprotective-response
#12
Lin Luo, Yeru Chen, Hongyan Wang, Shengcun Wang, Kaihua Liu, Xin Li, Xiu Jun Wang, Xiuwen Tang
The present study was undertaken to investigate the possible protective effect of mitogen-activated protein kinase phosphatase 1 (Mkp-1) on toxin-induced hepatic injury. Here, we uncovered a positive feedback loop between Mkp-1, a dual threonine/tyrosine phosphatase, and nuclear factor erythroid 2-related factor 2 (Nrf2), a crucial regulator of the defense system in the liver. Mkp-1-/- mice exhibited decreased protein levels of Nrf2, phase II gene products, and reduced glutathione (GSH) in the liver. Induction of detoxifying enzymes by the Nrf2 activator butylated hydroxyanisole (BHA) or sulforaphane, was attenuated in the liver and small intestines of Mkp-1-/- mice, indicating that the Nrf2 signaling pathway is impaired as a result of Mkp-1 deficiency...
February 1, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29226622/pde4-inhibitor-rolipram-inhibits-the-expression-of-microsomal-prostaglandin-e-synthase-1-by-a-mechanism-dependent-on-map-kinase-phosphatase-1
#13
Lauri Tuure, Mari Hämäläinen, Eeva Moilanen
Phosphodiesterase-4 (PDE4) inhibitors have recently been introduced to the treatment of COPD and psoriatic arthritis. Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme synthesizing PGE2 , the most abundant prostanoid related to inflammation and inflammatory pain. mPGES-1 is a potential drug target for novel anti-inflammatory treatments aiming at an improved safety profile as compared to NSAIDs. Here we investigated the effect of the PDE4 inhibitor rolipram on the expression of mPGES-1 in macrophages; and a potential mediator role in the process for MAP kinase phosphatase-1 (MKP-1) which is an endogenous factor limiting the activity of the proinflammatory MAP kinases p38 and JNK...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29165873/andrographolide-inhibits-hypoxia-induced-hypoxia-inducible-factor-1%C3%AE-and-endothelin-1-expression-through-the-heme-oxygenase-1-co-cgmp-mkp-5-pathways-in-ea-hy926-cells
#14
Hung-Chih Lin, Shih-Li Su, Wan-Chun Lin, Ai-Hsuan Lin, Ya-Chen Yang, Chong-Kuei Lii, Haw-Wen Chen
Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1...
March 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29143999/microrna-27a-3p-inhibits-cell-viability-and-migration-through-down-regulating-dusp16-in-hepatocellular-carcinoma
#15
Jin-Mao Li, Jun Zhou, Zhen Xu, Hai-Jin Huang, Min-Jiang Chen, Jian-Song Ji
MicroRNA (miRNA or miR) has been shown to play an important role in the initiation and development in many different cancers. Here, we demonstrated down-regulated expression of miR-27a-3p in hepatocellular carcinoma (HCC) tissues in comparison with that in adjacent normal liver tissues based on the TCGA database. Cells viability and apoptosis was measured by CCK-8 and flow cytometry assay. Cell invasion and migration was measured by Transwell and wound healing assay. The effect of miR-27a-3p on DUSP16 expression was evaluated by luciferase assays, and western blot assay...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29141025/suppression-of-inflammatory-and-infection-responses-in-lung-macrophages-by-eucalyptus-oil-and-its-constituent-1-8-cineole-role-of-pattern-recognition-receptors-trem-1-and-nlrp3-the-map-kinase-regulator-mkp-1-and-nf%C3%AE%C2%BAb
#16
Niket Yadav, Harish Chandra
Eucalyptus oil (EO) used in traditional medicine continues to prove useful for aroma therapy in respiratory ailments; however, there is a paucity of information on its mechanism of action and active components. In this direction, we investigated EO and its dominant constituent 1,8-cineole (eucalyptol) using the murine lung alveolar macrophage (AM) cell line MH-S. In an LPS-induced AM inflammation model, pre-treatment with EO significantly reduced (P ≤0.01or 0.05) the pro-inflammatory mediators TNF-α, IL-1 (α and β), and NO, albeit at a variable rate and extent; 1,8-cineole diminished IL-1 and IL-6...
2017: PloS One
https://www.readbyqxmd.com/read/29128158/mitogen-activated-protein-kinase-regulation-in-hepatic-metabolism
#17
REVIEW
Ahmed Lawan, Anton M Bennett
The mitogen-activated protein kinases (MAPKs) participate in a multitude of processes that control hepatic metabolism. The liver regulates glucose and lipid metabolism, and under pathophysiological conditions such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) these processes become dysfunctional. Stress responses activate the hepatic MAPKs, and this is thought to impair insulin action and lipid metabolism. The MAPKs also activate the MAPK phosphatases (MKPs) which oppose their actions...
December 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29109832/cardioprotective-effect-of-resveratrol-in-a-postinfarction-heart-failure-model
#18
Adam Riba, Laszlo Deres, Balazs Sumegi, Kalman Toth, Eszter Szabados, Robert Halmosi
Despite great advances in therapies observed during the last decades, heart failure (HF) remained a major health problem in western countries. In order to further improve symptoms and survival in patients with heart failure, novel therapeutic strategies are needed. In some animal models of HF resveratrol (RES), it was able to prevent cardiac hypertrophy, contractile dysfunction, and remodeling. Several molecular mechanisms are thought to be involved in its protective effects, such as inhibition of prohypertrophic signaling molecules, improvement of myocardial Ca2+ handling, regulation of autophagy, and the reduction of oxidative stress and inflammation...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29100381/dusp4-is-associated-with-increased-resistance-against-anti-her2-therapy-in-breast-cancer
#19
Otília Menyhart, Jan Budczies, Gyöngyi Munkácsy, Francisco J Esteva, András Szabó, Teresa Puig Miquel, Balázs Győrffy
The majority of patients develop resistance against suppression of HER2-signaling mediated by trastuzumab in HER2 positive breast cancer (BC). HER2 overexpression activates multiple signaling pathways, including the mitogen-activated protein kinase (MAPK) cascade. MAPK phosphatases (MKPs) are essential regulators of MAPKs and participate in many facets of cellular regulation, including proliferation and apoptosis. We aimed to identify whether differential MKPs are associated with resistance to targeted therapy in patients previously treated with trastuzumab...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29077400/structural-and-dynamic-insights-into-the-mechanism-of-allosteric-signal-transmission-in-erk2-mediated-mkp3-activation
#20
Chang Lu, Xin Liu, Chen-Song Zhang, Haipeng Gong, Jia-Wei Wu, Zhi-Xin Wang
The mitogen-activated protein kinases (MAPKs) are key components of cellular signal transduction pathways, which are down-regulated by the MAPK phosphatases (MKPs). Catalytic activity of the MKPs is controlled both by their ability to recognize selective MAPKs and by allosteric activation upon binding to MAPK substrates. Here, we use a combination of experimental and computational techniques to elucidate the molecular mechanism for the ERK2-induced MKP3 activation. Mutational and kinetic study shows that the334 FNFM337 motif in the MKP3 catalytic domain is essential for MKP3-mediated ERK2 inactivation and is responsible for ERK2-mediated MKP3 activation...
November 21, 2017: Biochemistry
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