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p38 MAPKs

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https://www.readbyqxmd.com/read/29049722/a-ppar-gamma-agonist-rosiglitazone-suppresses-fibrotic-response-in-human-pterygium-fibroblasts-by-modulating-the-p38-mapk-pathway
#1
Selikem Abla Nuwormegbe, Joon Hyung Sohn, Sun Woong Kim
Purpose: Fibroblast activation may play an important role in pterygium progression. Synthetic peroxisome proliferator-activated receptor γ (PPAR-γ) ligands have been shown to be effective antifibrotic agents against transforming growth factor β1 (TGF-β1) induced fibrosis in several tissues. We aimed to investigate the antifibrotic effects of the PPAR-γ ligand rosiglitazone in pterygium fibroblasts and the underlying mechanisms. Methods: Profibrotic activation was induced by TGF-β1 in primary cultured human pterygium fibroblasts and the effect of rosiglitazone treatment on α-smooth muscle actin (α-SMA), and extra cellular matrix proteins synthesis was detected by western blotting, real-time PCR, immunostaining, and flow cytometry...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29048662/capsaicin-inhibits-proliferation-and-induces-apoptosis-in-osteosarcoma-cell-lines-via-the-mitogen%C3%A2-activated-protein-kinase-pathway
#2
Yuan Zhang, Xu Deng, Tao Lei, Chang Yu, Yang Wang, Guosheng Zhao, Xiaoji Luo, Ke Tang, Zhengxue Quan, Dianming Jiang
Capsaicin, a pungent molecular compound present in many hot peppers, exerts anticancer activities against various human cancer cell lines by inducing apoptosis. However, the effects of capsaicin on human osteosarcoma (OS) as well as the related mechanisms remain to be fully elucidated. In the present study, the anticancer effects of capsaicin on 3 human OS cell lines (MG63, 143B and HOS) were investigated. Various concentrations of capsaicin (50-300 µM) effectively decreased cell viability in all 3 OS cell lines in a dose-dependent manner...
September 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29047459/protostemonine-effectively-attenuates-lipopolysaccharide-induced-acute-lung-injury-in-mice
#3
Ya-Xian Wu, Hui-Qiong He, Yun-Juan Nie, Yun-He Ding, Lei Sun, Feng Qian
Protostemonine (PSN) is the main anti-inflammatory alkaloid extracted from the roots of Stemona sessilifolia (known as "Baibu" in traditional Chinese medicine). Here, we reported the inhibitory effects of PSN on lipopolysaccharide (LPS)-induced macrophage activation in vitro and LPS-induced acute lung injury in mice. Macrophage cell line RAW264.7 cells and mouse bone marrow-derived macrophages (BMDMs) were treated with PSN (1, 3, 10, 30 and 100 μmol/L) for 0.5 h and then challenged with LPS (0.1 μg/mL) for 24 h...
October 19, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29047406/loss-of-mkp-5-promotes-myofiber-survival-by-activating-stat3-bcl-2-signaling-during-regenerative-myogenesis
#4
Kisuk Min, Ahmed Lawan, Anton M Bennett
BACKGROUND: The mitogen-activated protein kinases (MAPKs) have been shown to be involved in regulating myofiber survival. In skeletal muscle, p38 MAPK and JNK are negatively regulated by MAPK phosphatase-5 (MKP-5). During muscle regeneration, MKP-5 is downregulated, thereby promoting p38 MAPK/JNK signaling, and subsequent repair of damaged muscle. Mice lacking MKP-5 expression exhibit enhanced regenerative myogenesis. However, the effect of MKP-5 on myofiber survival during regeneration is unclear...
October 18, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/29046637/meclizine-prevents-ovariectomy-induced-bone-loss-and-inhibits-osteoclastogenesis-partially-by-upregulating-pxr
#5
Jiachao Guo, Weijin Li, Yingxing Wu, Xingzhi Jing, Junming Huang, Jiaming Zhang, Wei Xiang, Ranyue Ren, Zhengtao Lv, Jun Xiao, Fengjing Guo
Pregnane X receptor (PXR) which belongs to the nuclear hormone receptor superfamily plays vital roles in several biological functions, especially in the inflammatory procedure. Besides that, PXR is revealed by recent studies to have essential effects on bone tissue. As an agonist of PXR, meclizine is a piperazine-derived histamine H1 antagonist, and has been frequently used for prevention and treatment of vomiting and nausea. Because osteoclastogenesis is characterized by the activation of inflammation-related signaling pathways, we speculated that meclizine may affect formation and function of osteoclast...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29046261/cinnamaldehyde-induces-fat-cell-autonomous-thermogenesis-and-metabolic-reprogramming
#6
Juan Jiang, Margo P Emont, Heejin Jun, Xiaona Qiao, Jiling Liao, Dong-Il Kim, Jun Wu
OBJECTIVE: Cinnamaldehyde (CA) is a food compound that has previously been observed to be protective against obesity and hyperglycemia in mouse models. In this study, we aimed to elucidate the mechanisms behind this protective effect by assessing the cell-autonomous response of primary adipocytes to CA treatment. METHODS: Primary murine adipocytes were treated with CA and thermogenic and metabolic responses were assessed after both acute and chronic treatments. Human adipose stem cells were differentiated and treated with CA to assess whether the CA-mediated signaling is conserved in humans...
September 1, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29045529/impact-of-genetic-variations-in-the-mapk-signaling-pathway-on-outcome-in-metastatic-colorectal-cancer-patients-treated-with-first-line-folfiri-and-bevacizumab-data-from-fire-3-and-tribe-trials
#7
M D Berger, S Stintzing, V Heinemann, D Yang, S Cao, Y Sunakawa, Y Ning, S Matsusaka, S Okazaki, Y Miyamoto, M Suenaga, M Schirripa, S Soni, W Zhang, A Falcone, F Loupakis, H-J Lenz
Background: The MAPK-interacting kinase 1 (MKNK1) is localized downstream of the RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway. Through phosphorylation MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a key player in translational control, whose expression is often upregulated in metastatic colorectal cancer patients (mCRC). Preclinical data suggest that MKNK1 increases angiogenesis by upregulating angiogenic factors. We therefore hypothesize that variations in the MKNK1 gene predict outcome in mCRC patients treated with first-line FOLFIRI and bevacizumab (bev)...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045288/effects-of-anti-inflammatory-medications-in-patients-with-coronary-artery-disease-a-focus-on-losmapimod
#8
Bradley Tun, William H Frishman
Inflammation plays an integral role in atherogenesis and the pathogenesis of coronary artery disease (CAD). The question remains as to whether targeted inhibition of specific pathways of inflammation will have any clinical benefits in CAD. In this article we will review p38 mitogen-activated protein kinase (p38 MAPK), one of the key sensors of cellular stress that plays an important role in the inflammatory cascade. In addition, we will review losmapimod, a reversible competitive inhibitor of the α and β isoforms of p38 MAPK, and its efficacy when added to standard of care in patients hospitalized with myocardial infarction...
October 17, 2017: Cardiology in Review
https://www.readbyqxmd.com/read/29042963/warm-sparse-dense-wave-inhibits-cartilage-degradation-in-papain-induced-osteoarthritis-through-the-mitogen-activated-protein-kinase-signaling-pathway
#9
Munan Lin, Yanhong Lin, Xihai Li, Wenna Liang, Shuiliang Wang, Jiansheng Liu, Xianxiang Liu, Lidian Chen, Yin Qin
Cartilage degradation is an important in the pathogenesis of osteoarthritis (OA). Abnormal activation of the mitogen-activated protein kinase (MAPK) signaling pathway in chondrocytes promotes an inflammatory response, resulting in the release of chondral matrix-degrading enzymes that accelerate the degradation of cartilage. As a non-pharmaceutical and non-invasive physical therapy regimen, warm sparse-dense wave (WSDW) has been successfully used for the treatment of OA. However, it remains unclear whether WSDW inhibits cartilage degradation in OA through the MAPK signaling pathway...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042302/attenuation-of-pseudomonas-aeruginosa-quorum-sensing-virulence-and-biofilm-formation-by-extracts-of-andrographis-paniculata
#10
Malabika Banerjee, Soumitra Moulick, Kunal Kumar Bhattacharya, Debaprasad Parai, Subrata Chattopadhyay, Samir Kumar Mukherjee
Quorum-sensing (QS) is known to play an essential role in regulation of virulence factors and toxins during Pseudomonas aeruginosa infection which may frequently cause antibiotic resistance and hostile outcomes of inflammatory injury. Therefore, it is an urgent need to search for a novel agent with low risk of resistance development that can target QS and inflammatory damage prevention as well. Andrographis paniculata, a herbaceous plant under the family Acanthaceae, native to Asian countries and also cultivated in Scandinavia and some parts of Europe, has a strong traditional usage with its known antibacterial, anti-inflammatory, antipyretic, antiviral and antioxidant properties...
October 14, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29040306/micheliolide-suppresses-lps-induced-neuroinflammatory-responses
#11
Zhaomeng Sun, Guodong Li, Tanjun Tong, Jun Chen
Microglia-involved neuroinflammation is thought to promote brain damage in various neurodegenerative disorders. Thus, inhibition of microglial over-activation may have a therapeutic benefit for the treatment of neurodegenerative disorders. Micheliolide (MCL) is a sesquiterpene lactone which inhibits various inflammatory response. However, whether MCL can inhibit neuroinflammation caused by LPS-activated BV2 microglia has not yet been explored. In this study, we demonstrated that treatment of BV2 cells with MCL significantly repressed LPS-stimulated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, as well as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) induction...
2017: PloS One
https://www.readbyqxmd.com/read/29039574/tgf-%C3%AE-1-induced-cell-migration-in-pancreatic-carcinoma-cells-is-rac1-and-nox4-dependent-and-requires-rac1-and-nox4-dependent-activation-of-p38%C3%A2-mapk
#12
David Witte, Tobias Bartscht, Roland Kaufmann, Ralph Pries, Utz Settmacher, Hendrik Lehnert, Hendrik Ungefroren
Transforming growth factor (TGF)-β promotes epithelial-mesenchymal transition and cell invasion of cancer cells in part through the small GTPase RAC1. Since RAC1 can signal through reactive oxygen species (ROS), we probed the role of the ROS-producing NADPH oxidase (NOX) and p38 mitogen-activated protein kinase (MAPK) in mediating TGF-β1/RAC1-driven random cell migration (chemokinesis). Although the NOX isoforms NOX2, 4, 5, 6, and RAC1 were readily detectable by RT-PCR in pancreatic ductal adenocarcinoma (PDAC)-derived Panc1 and Colo357 cells, only NOX4 and RAC1 were expressed at higher levels comparable to those in peripheral blood monocytes...
October 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29039541/modulation-of-mitogen%C3%A2-activated-protein-kinase-attenuates-sepsis%C3%A2-induced-acute-lung-injury-in-acute-respiratory-distress-syndrome-rats
#13
Wei Fang, Shi-Xia Cai, Chuan-Lei Wang, Xiao-Xia Sun, Kun Li, Xiao-Wen Yan, Yun-Bo Sun, Xiao-Zhe Sun, Chuan-Kai Gu, Ming-Ying Dai, Hui-Ming Wang, Zhen Zhou
Sepsis is the most important predisposing cause inducing acute respiratory distress syndrome (ARDS); however, the mechanism of sepsis leading to the development of ARDS remains to be elucidated. Suppression of the mitogen‑activated protein kinase (MAPK) signal by blocking the phosphorylation of Jun N‑terminal kinase (JNK) and p38 in lung tissues could alleviate acute lung injury induced by sepsis. MAPK signaling may have a crucial role in development of the sepsis‑induced acute lung injury. The specific inhibitors of JNK and p38 MAPK, SP600125 and SB203580, were administrated by intragastric injection 4 h before induction of ARDS after cecal ligation and puncture (CLP)...
October 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29039451/anti-inhibitory-potential-of-an-ethanolic-extract-of-distromium-decumbens-on-pro-inflammatory-cytokine-production-in-pseudomonas-aeruginosa-lipopolysaccharide-stimulated-nasal-polyp-derived-fibroblasts
#14
Dae-Sung Lee, Chang-Min Lee, Seong Kook Park, Mi-Jin Yim, Jeong Min Lee, Grace Choi, Jong Su Yoo, Won-Kyo Jung, Saegwang Park, Su-Kil Seo, Won Sun Park, Il-Whan Choi
Marine algae are rich sources of biologically active compounds that may present useful leads in the development of pharmaceuticals, nutraceuticals, and functional foods. The main aim of this study was to identify the possible anti-inflammatory effects of Distromium decumbens in nasal polyp-derived fibroblasts (NPDFs) and its associated mechanism of action. NPDFs were stimulated by Pseudomonas aeruginosa lipopolysaccharide (PA-LPS) and treated with an ethanolic extract of Distromium decumbens (DDE). The production of interleukin-6 (IL-6) and IL-8 in the supernatant, the phosphorylation of mitogen-activated protein kinase (MAPK) molecules [extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase and p38 MAPK] and Akt, and the activation of nuclear factor-κB (NF-κB) were assayed in the PA-LPS-stimulated NPDFs untreated or treated with DDE...
October 11, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29039448/astragaloside-iv-attenuates-the-h2o2-induced-apoptosis-of-neuronal-cells-by-inhibiting-%C3%AE-synuclein-expression-via-the-p38-mapk-pathway
#15
Xiang Liu, Jun Zhang, Shibo Wang, Jinfu Qiu, Chao Yu
An oxidative stress insult is one of the principal causes of Parkinson's disease. Astragaloside IV (AS-IV), a constituent extracted from Astragalus membranaceus, has been demonstrated to exert antioxidant effects. However, the mechanisms responsible for the antioxidant properties and neuroprotective effects of AS-IV remain unclear. In this study, we examined the protective effects of AS-IV against the apoptosis of human neuronal cells (SH-SY5Y cells) induced by hydrogen peroxide (H2O2). The results revealed that AS-IV pre-treatment attenuated the H2O2‑induced loss of SH-SY5Y cells in a dose-dependent manner; AS-IV exerted significant protecitve effects by decreasing the apoptotic ratio and attenuating reactive oxygen species overproduction in H2O2-exposed SH-SY5Y cells...
September 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29037868/the-fungal-neurotoxin-penitrem-a-induces-the-production-of-reactive-oxygen-species-in-human-neutrophils-at-submicromolar-concentrations
#16
H F Berntsen, I L Bogen, M B Wigestrand, F Fonnum, S I Walaas, A Moldes-Anaya
Penitrem A is a fungal neurotoxin that recurrently causes intoxication in animals, and occasionally also in humans. We have previously reported that penitrem A induced the production of reactive oxygen species (ROS) in rat cerebellar granule cells, opening for a new mechanism of action for the neurotoxin. The aim of this study was to examine the potential of penitrem A to induce ROS production in isolated human neutrophil granulocytes, and to study possible mechanisms involved. Penitrem A significantly increased the production of ROS in human neutrophils at concentrations as low as 0...
October 13, 2017: Toxicology
https://www.readbyqxmd.com/read/29035884/protective-effects-of-pretreatment-with-quercetin-against-lipopolysaccharide-induced-apoptosis-and-the-inhibition-of-osteoblast-differentiation-via-the-mapk-and-wnt-%C3%AE-catenin-pathways-in-mc3t3-e1-cells
#17
Chun Guo, Rui-Juan Yang, Ke Jang, Xiao-Ling Zhou, Yu-Zhen Liu
BACKGROUND/AIMS: Quercetin, a flavonoid found in onions and other vegetables, has potential inhibitory effects on bone resorption in vivo and in vitro. In our previous study, we found that quercetin treatment reversed lipopolysaccharide (LPS)-induced inhibition of osteoblast differentiation through the mitogen-activated protein kinase (MAPK) pathway in MC3T3-E1 cells. In this study, we investigated the underlying mechanisms of pretreatment with quercetin on apoptosis and the inhibition of osteoblast differentiation in MC3T3-E1 cells induced by LPS...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29035881/activation-of-signaling-cascades-by-weak-extremely-low-frequency-electromagnetic-fields
#18
Einat Kapri-Pardes, Tamar Hanoch, Galia Maik-Rachline, Manuel Murbach, Patricia L Bounds, Niels Kuster, Rony Seger
BACKGROUND/AIMS: Results from recent studies suggest that extremely low frequency magnetic fields (ELF-MF) interfere with intracellular signaling pathways related to proliferative control. The mitogen-activated protein kinases (MAPKs), central signaling components that regulate essentially all stimulated cellular processes, include the extracellular signal-regulated kinases 1/2 (ERK1/2) that are extremely sensitive to extracellular cues. Anti-phospho-ERK antibodies serve as a readout for ERK1/2 activation and are able to detect minute changes in ERK stimulation...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29034730/corydaline-inhibits-enterovirus-71-replication-by-regulating-cox-2-expression
#19
Hui-Qiang Wang, Jin Hu, Hai-Yan Yan, Shuo Wu, Yu-Huan Li
Enterovirus 71 (EV71) is a huge threat to the worldwide public health and there is no approved antiviral drug for EV71-induced disease therapy. Corydaline exists antiallergic and antinociceptive activities, but the anti-EV71 activity of corydaline is still not reported. In this study, corydaline could suppress the expression of viral structural and non-structural proteins. Furthermore, corydaline inhibits EV71 replication by suppressing the COX-2 expression and the phosphorylation of JNK MAPK and P38 MAPK but not ERK MAPK in vitro...
October 15, 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/29033931/plasmodium-berghei-nk65-in-combination-with-ifn-%C3%AE-induces-endothelial-glucocorticoid-resistance-via-sustained-activation-of-p38-and-jnk
#20
Karolina A Zielińska, Lode de Cauwer, Sofie Knoops, Kristof Van der Molen, Alexander Sneyers, Jonathan Thommis, J Brian De Souza, Ghislain Opdenakker, Karolien De Bosscher, Philippe E Van den Steen
Malaria-associated acute respiratory distress syndrome (MA-ARDS) is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs) have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ) and Plasmodium berghei NK65 (PbNK65)...
2017: Frontiers in Immunology
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