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https://www.readbyqxmd.com/read/28299397/suppression-of-cytokine-production-by-glucocorticoids-is-mediated-by-mkp-1-in-human-lung-epithelial-cells
#1
Tiina Keränen, Eeva Moilanen, Riku Korhonen
Mitogen-activated protein kinase phosphatase 1 (MKP-1) expression is induced by inflammatory factors and serves as an endogenous p38 MAPK suppressor to limit inflammatory response. Glucocorticoids are very effective anti-inflammatory drugs and they are used for the treatment of many inflammatory diseases, such as asthma and COPD. We investigated the role of MKP-1 in the inhibition of cytokine production by dexamethasone in human A549 bronchial epithelial cells. We found that dexamethasone increased MKP-1 expression, inhibited p38 MAPK phosphorylation, and suppressed TNF and MIP-3α production in A549 cells...
March 15, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28252035/regulation-of-atypical-map-kinases-erk3-and-erk4-by-the-phosphatase-dusp2
#2
Maria Perander, Rania Al-Mahdi, Thomas C Jensen, Jennifer A L Nunn, Hanne Kildalsen, Bjarne Johansen, Mads Gabrielsen, Stephen M Keyse, Ole-Morten Seternes
The atypical MAP kinases ERK3 and ERK4 are activated by phosphorylation of a serine residue lying within the activation loop signature sequence S-E-G. However, the regulation of ERK3 and ERK4 phosphorylation and activity is poorly understood. Here we report that the inducible nuclear dual-specificity MAP kinase phosphatase (MKP) DUSP2, a known regulator of the ERK and p38 MAPKs, is unique amongst the MKP family in being able to bind to both ERK3 and ERK4. This interaction is mediated by a conserved common docking (CD) domain within the carboxyl-terminal domains of ERK3 and ERK4 and the conserved kinase interaction motif (KIM) located within the non-catalytic amino terminus of DUSP2...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28238855/mkp-1-negatively-regulates-lps-mediated-il-1%C3%AE-production-through-p38-activation-and-hif-1%C3%AE-expression
#3
Harvinder Talwar, Christian Bauerfeld, Mohamad Bouhamdan, Pershang Farshi, Yusen Liu, Lobelia Samavati
Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine that plays a major role in inflammatory diseases as well as cancer. The inflammatory response after Toll-like receptor (TLR) 4 activation is tightly regulated through phosphorylation of MAP kinases, including p38 and JNK pathways. The activation of MAP kinases is negatively regulated by MAPK phosphatases (MKPs). MKP-1 preferentially dephosphorylates p38 and JNK. IL-1β is regulated through the activation of MAPK, including p38 as well as several transcription factors...
February 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28238828/dilodendron-bipinnatum-radlk-inhibits-pro-inflammatory-mediators-through-the-induction-of-mkp-1-and-the-down-regulation-of-mapkp38-jnk-nf-%C3%AE%C2%BAb-pathways-and-cox-2-in-lps-activated-raw-264-7-cells
#4
Ruberlei Godinho de Oliveira, Geovane Roberto de Campos Castilho, André Luiz da Cunha, Fábio Miyajima, Domingos Tabajara de Oliveira Martins
ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Dilodendron bipinnatum Radlk. (Sapindaceae), a tree native to Pantanal of Mato Grosso, Brazil, popularly known as "mulher-pobre" (poor woman), has been historically used by the locals, after decoction and maceration, for the treatment of inflammatory conditions. We have recently shown that these preparations indeed possess anti-inflammatory properties, which are mediated by the inhibition of cell migration and the modulation of Th1 and Th2 cytokines...
February 23, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28224917/regulation-of-the-wheat-map-kinase-phosphatase-1-by-14-3-3-proteins
#5
Mouna Ghorbel, Valérie Cotelle, Chantal Ebel, Ikram Zaidi, Mélanie Ormancey, Jean-Philippe Galaud, Moez Hanin
Plant MAP kinase phosphatases (MKPs) are major regulators of MAPK signaling pathways and play crucial roles in controlling growth, development and stress responses. The presence of several functional domains in plant MKPs such as a dual specificity phosphatase catalytic domain, gelsolin, calmodulin-binding and serine-rich domains, suggests that MKPs can interact with distinct cellular partners, others than MAPKs. In this report, we identified a canonical mode I 14-3-3-binding motif (574KLPSLP579) located at the carboxy-terminal region of the wheat MKP, TMKP1...
April 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28170447/comparison-of-mkp-and-bsk-h-media-for-the-cultivation-and-isolation-of-borrelia-burgdorferi-sensu-lato
#6
Eva Ružić-Sabljić, Vera Maraspin, Daša Stupica, Tereza Rojko, Petra Bogovič, Franc Strle, Tjaša Cerar
The isolation of B. burgdorferi sensu lato requires the use of complex cultivation media. The aim of the study was to compare the usefulness of BSK-H (a commercial medium produced by HiMedia, India) and MKP medium. MKP and BSK-H media were prepared in accordance with the relevant protocols. Borrelia strains and skin culture biopsies were simultaneously inoculated into both media, incubated and checked for growth. Borrelial growth characteristics, isolation rates and characteristics of the isolated borreliae were analysed and compared...
2017: PloS One
https://www.readbyqxmd.com/read/28161489/antiproliferative-effects-of-bortezomib-in-endothelial-cells-transformed-by-viral-g-protein-coupled-receptor-associated-to-kaposi-s-sarcoma
#7
A Suares, M Mori Sequeiros Garcia, C Paz, V González-Pardo
The Kaposi's Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi Sarcoma. We have previously demonstrated that the proteasome inhibitor Bortezomib inhibits NF-κB pathway, which is required for tumor maintenance in endothelial cells that express vGPCR (vGPCR cells). In this work, we further investigated Bortezomib anti-proliferative mechanism of action. We demonstrated that Bortezomib decreases vGPCR cell number in a dose-dependent manner and induces cell morphology changes...
February 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28158298/administration-of-bovine-casein-derived-peptide-prevents-cognitive-decline-in-alzheimer-disease-model-mice
#8
Li-Juan Min, Yodai Kobayashi, Masaki Mogi, Kana Tsukuda, Akio Yamada, Koji Yamauchi, Fumiaki Abe, Jun Iwanami, Jin-Zhong Xiao, Masatsugu Horiuchi
There is a growing interest in identifying natural food ingredients that may serve to prevent dementia such as that due to Alzheimer disease (AD). Peptides derived from food proteins have been demonstrated to have various physiological activities such as a hypotensive action. Recent findings have indicated possible associations of hypertension with AD progression, and suggest that angiotensin converting enzyme (ACE) inhibitors with potential to pass through the blood brain barrier (BBB) may reduce the risk of AD...
2017: PloS One
https://www.readbyqxmd.com/read/28154014/a-tumor-cell-selective-inhibitor-of-mitogen-activated-protein-kinase-phosphatases-sensitizes-breast-cancer-cells-to-lymphokine-activated-killer-cell-activity
#9
Christof T Kaltenmeier, Laura L Vollmer, Lawrence A Vernetti, Lindsay Caprio, Keanu Davis, Vasiliy N Korotchenko, Billy W Day, Michael Tsang, Keren I Hulkower, Michael T Lotze, Andreas Vogt
Dual specificity mitogen activated protein kinase (MAPK) phosphatases (DUSP-MKPs) have been hypothesized to maintain cancer cell survival by buffering excessive MAPK signaling caused by upstream activating oncogenic products. A large and diverse body of literature suggests that genetic depletion of DUSP-MKPs can reduce tumorigenicity, suggesting that hyperactivating MAPK signaling by DUSP-MKP inhibitors could be a novel strategy to selectively affect the transformed phenotype. Through in vivo structure activity relationship studies in transgenic zebrafish we recently identified a hyperactivator of Fibroblast Growth Factor signaling (BCI-215) that is devoid of developmental toxicity and restores defective MAPK activity caused by overexpression of DUSP1 and DUSP6 in mammalian cells...
February 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28130620/extranodal-spread-is-associated-with-recurrence-and-poor-survival-in-stage-iii-cutaneous-melanoma-patients
#10
Thomas R Crookes, Richard A Scolyer, Serigne Lo, Martin Drummond, Andrew J Spillane
BACKGROUND: Inconsistent data suggests extranodal spread (ENS) is an adverse prognostic factor in Stage III melanoma patients but it remains contentious. By rigorously matching cohorts, this study sought to clarify associations with recurrence and survival. METHODS: Melanoma patients with lymph node metastases (AJCC Stage III), with or without ENS, sub-classified on the basis of known (MKP) or unknown primary (MUP), were identified from a single institution prospective database...
January 27, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28111292/disruption-of-brain-mek-erk-sequential-phosphorylation-and-activation-during-midazolam-induced-hypnosis-in-mice-roles-of-gabaa-receptor-mek1-inactivation-and-phosphatase-mkp-3
#11
María Álvaro-Bartolomé, Glòria Salort, Jesús A García-Sevilla
Midazolam is a positive allosteric modulator at GABAA receptor that induces a short hypnosis and neuroplasticity, in which the sequential phosphorylation of MEK1/2 and ERK1/2 was shown to play a role. This study investigated the parallel activation of p-MEK and p-ERK and regulatory mechanisms induced by midazolam through the stimulation of GABAA receptors in the mouse brain. During the time course of midazolam (60mg/kg)-induced sleep in mice (lasting for about 2h) p-Ser217/221 MEK1/2 was increased (+146% to +258%) whereas, unexpectedly, p-Tyr204/Thr202 ERK1/2 was found decreased (-16% to -38%), revealing uncoupling of MEK to ERK signals in various brain regions...
April 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28110053/development-and-optimization-of-an-in-vitro-cultivation-protocol-allows-for-isolation-of-borrelia-miyamotoi-from-patients-with-hard-tick-borne-relapsing-fever
#12
Joris Koetsveld, Nadezhda M Kolyasnikova, Alex Wagemakers, Marina G Toporkova, Denis S Sarksyan, Anneke Oei, Alexander E Platonov, Joppe W Hovius
OBJECTIVES: Borrelia miyamotoi has been shown to infect humans in Eurasia and North America causing hard tick-borne relapsing fever (HTBRF). In vitro cultivation of B. miyamotoi was described recently; however, clinical isolation of relapsing fever Borrelia is cumbersome. Our aim was to develop a straightforward protocol enabling B. miyamotoi isolation directly from blood of patients. METHODS: MKP-F media, with or without anticoagulants, or blood from healthy human volunteers, was spiked with B...
January 18, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28096466/a-phosphoproteomic-screen-identifies-a-guanine-nucleotide-exchange-factor-for-rab3a-as-a-map-kinase-phosphatase-5-regulated-map-kinase-target-in-il-6-secretion-and-myogenesis
#13
Hojin Lee, Kisuk Min, Jae-Sung Yi, Hao Shi, Woochul Chang, Leandra Jackson, Anton M Bennett
The mitogen-activated protein kinases (MAPKs) have been shown to regulate skeletal muscle function. Previously, we showed that MAPK phosphatase-5 (MKP-5) negatively regulates myogenesis and regeneration of skeletal muscle through inhibition of p38 MAPK and c-Jun N-terminal kinase (JNK). However, the identity and contribution of MKP-5-dependent MAPK targets in the regulation of skeletal muscle function and regenerative myogenesis has not been established. In order to identify MKP-5-dependent MAPK substrates in skeletal muscle, we performed a global differential phospho-MAPK substrate screen in regenerating skeletal muscles of wild type and MKP-5-deficient mice...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28053233/dual-specificity-phosphatase-5-controls-the-localized-inhibition-propagation-and-transforming-potential-of-erk-signaling
#14
Andrew M Kidger, Linda K Rushworth, Julia Stellzig, Jane Davidson, Christopher J Bryant, Cassidy Bayley, Edward Caddye, Tim Rogers, Stephen M Keyse, Christopher J Caunt
Deregulated extracellular signal-regulated kinase (ERK) signaling drives cancer growth. Normally, ERK activity is self-limiting by the rapid inactivation of upstream kinases and delayed induction of dual-specificity MAP kinase phosphatases (MKPs/DUSPs). However, interactions between these feedback mechanisms are unclear. Here we show that, although the MKP DUSP5 both inactivates and anchors ERK in the nucleus, it paradoxically increases and prolongs cytoplasmic ERK activity. The latter effect is caused, at least in part, by the relief of ERK-mediated RAF inhibition...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27997807/roflumilast-n-oxide-in-combination-with-formoterol-enhances-the-anti-inflammatory-effect-of-dexamethasone-in-asm-cells
#15
Brijeshkumar S Patel, Md Mostafizur Rahman, Gina Baehring, Dikaia Xenaki, Francesca Su-May Tang, Brian G Oliver, Alaina J Ammit
Roflumilast is an orally active phosphodiesterase 4 (PDE4) inhibitor approved for use in chronic obstructive pulmonary disease. Roflumilast N-oxide (RNO) is the active metabolite of roflumilast and has demonstrated anti-inflammatory impact in vivo and in vitro. To date, the effect of RNO on the synthetic function of airway smooth muscle (ASM) cells is unknown. We address this herein and investigate the effect of RNO on β2-adrenoceptor-mediated, cAMP-dependent responses in ASM cells in vitro, and whether RNO enhances steroid-induced repression of inflammation...
December 20, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27958388/map-kinase-phosphatase-2-deficient-mice-develop-attenuated-experimental-autoimmune-encephalomyelitis-through-regulating-dendritic-cells-and-t-cells
#16
Mark Barbour, Robin Plevin, Hui-Rong Jiang
Mitogen-activated protein kinase phosphatases (MKPs) play key roles in inflammation and immune mediated diseases. Here we investigated the mechanisms by which MKP-2 modulates central nervous system (CNS) inflammation in experimental autoimmune encephalomyelitis (EAE). Our results show that MKP-2 mRNA levels in the spinal cord and lymphoid organs of EAE mice were increased compared with naive controls, indicating an important role for MKP-2 in EAE development. Indeed, MKP-2(-/-) mice developed reduced EAE severity, associated with diminished CNS immune cell infiltration, decreased proinflammatory cytokine production and reduced frequency of CD4(+) and CD8(+) T cells in spleens and lymph nodes...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27913746/anti-trachea-inflammatory-effects-of-diosgenin-from-dioscorea-nipponica-through-interactions-with-glucocorticoid-receptor-%C3%AE
#17
Yang Junchao, Wang Zhen, Wang Yuan, Xu Liying, Jiang Libin, Zhu Yuanhong, Zhao Wei, Chen Ruilin, Zhai Lu
Asthma is a heterogeneous disease characterized by symptoms of chronic inflammation and airway structural and functional changes. It affects about 300 million people worldwide and causes 250 000 deaths annually, but its symptoms can be greatly relieved by regular use of inhaled glucocorticoids (GCs). GCs exert their function through interacting with glucocorticoid receptors (GRs). Diosgenin is a naturally occurring steroidal saponin abundantly present in many medicinal plants, including Dioscorea nipponica, which shares a similar steroidal structure with GC...
December 2, 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27852250/impaired-anti-inflammatory-action-of-glucocorticoid-in-neutrophil-from-patients-with-steroid-resistant-asthma
#18
Meijia Wang, Pengfei Gao, Xiaojie Wu, Yuetao Chen, Yikuan Feng, Qun Yang, Yongjian Xu, Jianping Zhao, Jungang Xie
BACKGROUND: Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared to SR asthmatics. METHODS: Adults with asthma (n = 38) were classified as SR or SS based on changes in lung FEV1% following a one-month inhaled corticosteroid (ICS) treatment...
November 16, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27783995/mkp-1-attenuates-lps-induced-blood-testis-barrier-dysfunction-and-inflammatory-response-through-p38-and-i%C3%AE%C2%BAb%C3%AE-pathways
#19
Yiqing Pan, Yue Liu, Li Wang, Feng Xue, Yanqin Hu, Ran Hu, Chen Xu
Sertoli cells create a local tolerogenic microenvironment to maintain testicular immune privilege especially through the formation of a blood-testis barrier (BTB). However, the molecular mechanisms underlying the immune modulation function and BTB dynamics of Sertoli cells remained elusive. MAP phosphatase (MKP)-1 acts as a crucial negative regulator of the inflammatory response. Nevertheless, the role of MKP-1 in regulating Sertoli cells has not been elucidated. In this study, we have for the first time uncovered distinct cellular localization of MKP-1 in the cells at different stages of mouse testis, and the level of MKP-1 expression was significantly up-regulated by LPS-induced acute testis inflammation...
October 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27771897/profiling-of-signaling-proteins-in-penumbra-after-focal-photothrombotic-infarct-in-the-rat-brain-cortex
#20
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
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