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p38 mapk

Airi Ohsaki, Yuki Miyano, Rei Tanaka, Sei-Ichi Tanuma, Shuji Kojima, Mitsutoshi Tsukimoto
Skin inflammation is caused by excessive production of cytokines and chemokines in response to an external stimulus, such as radiation, but the mechanisms involved are not completely understood. Here, we report a novel mechanism of γ-irradiation-induced IL-6 production mediated by P2Y11 receptors in epidermal cells. After irradiation of HaCaT cells derived from human epidermal keratinocytes with 5 Gy of γ-rays (137 Cs : 0.78 Gy/min), IL-6 production was unchanged at 24 h after γ-irradiation, but was increased at 48 h...
March 16, 2018: Biological & Pharmaceutical Bulletin
Xiangpeng Hu, Hongwei Kan, Alex Boye, Yufeng Jiang, Chao Wu, Yan Yang
The transforming growth factor (TGF)-β/Smad signaling pathway is involved in hepatocellular carcinoma development. Smad2 and Smad3 are phosphorylated following TGF-β1 stimulation and subsequently oligomerize with Smad4 to form the Smad2/3/4 complex, which translocates into the nucleus and regulates target genes, including plasminogen activator inhibitor type 1 (PAI1). Importin (Imp)7 and Imp8 are responsible for transporting phosphorylated (p)Smad2/3 and Smad4 into the nucleus. In our previous study, it was demonstrated that mitogen-activated protein kinase (MAPK) inhibitors, including inhibitors of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 could inhibit the transcription of PAI1, but ERK inhibitor had no significant effect on the phosphorylation of Smad2/3, and the formation of Smad2/3/4 complexes, which was different from the effect of JNK or p38 inhibitor...
April 2018: Oncology Letters
Yuqiu Zheng, Wenli Fang, Shengnuo Fan, Wang Liao, Ying Xiong, Shaowei Liao, Yi Li, Songhua Xiao, Jun Liu
Neurotropin (NTP) is a widely used drug in China and Japan mainly for the treatment of chronic pain and peripheral inflammation. Nevertheless, the effects of NTP on neuroinflammation have not been explored. In this study, we investigated the anti-inflammatory effects of NTP in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and its underlying mechanisms. BV-2 cells were pretreated with NTP for 12 h before exposure to LPS. The expression of pro-inflammatory cytokines (TNF-α and IL-6) were detected by RT-PCR and EILSA at mRNA and protein levels, respectively...
February 27, 2018: Journal of Pharmacological Sciences
Alba Bosquet, Josefa Girona, Sandra Guaita-Esteruelas, Mercedes Heras, Paula Saavedra-García, Neus Martínez-Micaelo, Lluís Masana, Ricardo Rodríguez-Calvo
AIMS: Fatty acid binding protein 4 (FABP4) inhibitors have been proposed as potential therapeutic approaches against insulin resistance-related inflammation and type 2 diabetes mellitus. However, the underlying molecular mechanisms by which these molecules drive these effects in skeletal muscle remain unknown. Here, we assessed whether the FABP4 inhibitor BMS309403 prevented lipid-induced endoplasmic reticulum (ER) stress-associated inflammation in skeletal muscle. MATERIALS AND METHODS: The BMS309403 treatment was assessed both in the skeletal muscle of high-fat diet (HFD)-fed mice and in palmitate-stimulated C2C12 myotubes...
March 14, 2018: Biochimica et Biophysica Acta
Jing Guo, Xiao Qiu, Luo Zhang, Rongfei Wei
Smad ubiquitylation regulatory factor 1 (Smurf1) has been identified to play a critical role in bone homeostasis, development, cell cycle regulation and tumorigenesis. However, the role of Smurf1 in macrophage proliferation, apoptosis and migration is still unclear. Here, we show that Smurf1 expression was elevated in LPS-induced RAW264.7 macrophage and mouse embryonic fibroblasts (MEFs). And we found that knockdown of Smurf1 suppresses macrophage proliferation but promotes apoptosis and migration. Furthermore, JNK and p38 MAPK signaling were upregulated in Smurf1-depleted cells...
March 15, 2018: Molecular Immunology
Md Moniruzzaman, Young-Won Chin, Jungsook Cho
Physalis alkekengi var. francheti is an indigenous herb well known for its anti-inflammatory, sedative, antipyretic, and expectorant properties. However, the information regarding the impacts of P. alkekengi fruits (PAF) in modulation of oxidative stress and learning memory are still unknown. This study therefore evaluated the antioxidant properties of ethyl acetate (EA) fraction of PAF and its impacts on learning and memory. The antioxidant activities of PAF were evaluated in LPS-induced BV2 microglial cells...
March 15, 2018: Cell Stress & Chaperones
Jinfeng Cui, Juan Wang, Shujuan Huang, Xiujuan Jiang, Yuehong Li, Wenxin Wu, Xianghong Zhang
Sterigmatocystin (ST), being a precursor of aflatoxin, is categorized as Group 2B carcinogen. Our previous studies found that both mismatch repair (MMR) pathways and p53 signaling pathway were involved in ST-induced G2 cell cycle arrest in human esophageal squamous epithelial cell line, HET-1A, in vitro. Studies showed that ERK, JNK and p38 signaling pathways played important roles in cell cycle arrest induced by several other carcinogens. However, the role of MAPK pathway and the links between the MMR and p53 signaling pathways in ST induced G2 phase arrest is still not clarified...
March 12, 2018: Food and Chemical Toxicology
Yaoming Peng, Jiabin Lin, Junyan Ma, Kaiqing Lin, Kaihong Xu, Jun Lin
S100 calcium-binding protein A6 (S100A6) is up-regulated in many malignancies and overexpression of S100A6 has been identified associated with proliferation, migration and invasion phenotype in several cancer cells. In the present study, we explored whether S100A6 plays a role in the development of endometriosis. Significantly higher levels of mRNA and protein expression of S100A6 were observed in ectopic endometrial tissues compared to eutopic and normal endometrial tissues. Silencing of S100A6 in ectopic endometrial stromal cells (ESCs) significantly inhibited cell viability, migration and invasion...
March 16, 2018: Gynecological Endocrinology
Yoshitoshi Kasuya, Hiroki Umezawa, Masahiko Hatano
Spinal cord injury (SCI) consists of three phases-acute, secondary, and chronic damages-and limiting the development of secondary damage possibly improves functional recovery after SCI. A major component of the secondary phase of SCI is regarded as inflammation-triggered events: induction of cytokines, edema, microglial activation, apoptosis of cells including oligodendrocytes and neurons, demyelination, formation of the astrocytic scar, and so on. Two major stress-activated protein kinases (SAPKs)-c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK)-are activated in various types of cells in response to cellular stresses such as apoptotic stimuli and inflammatory waves...
March 15, 2018: International Journal of Molecular Sciences
Yawen Li, Fangming Xiu, Zezhong Mou, Zhiwei Xue, Huanhui Du, Chunxue Zhou, Yan Li, Yongyu Shi, Shenyi He, Huaiyu Zhou
AIM: Exosomes are nanoscale membranous vesicles secreted by most cell types able to transfer bioactive molecules among cells, which play crucial roles in intercellular communication. We characterized the exosomes derived from Toxoplasma gondii (T. gondii) and detected the immune response in macrophages. METHODS: We used transmission electron microscopy, nanotracking analysis and western blotting to identify T. gondii exosomes. Functional experiments were performed in RAW264...
March 15, 2018: Nanomedicine
Luping Wang, Hushan Wang, Zongsheng Duan, Jian Zhang, Wenwen Zhang
This study investigated the protective effect ofgastrodin on cell apoptosis in rats hippocampus tissues induced by desflurane to explore its mechanism. A total of 36 rats were randomly divided into three groups: Blank control group (C group, n=12), desflurane anesthesia group (DF group, n=12) and gastrodin treatment group (GT group, n=12). Rats in DF group were treated with anesthesia using desflurane. Rats in GT group were treated with gavage using gastrodin and the same treatment as DF group. After the experiment, novel object recognition test and water maze test were performed...
March 2018: Experimental and Therapeutic Medicine
Ren-Hong Du, Hong-Bin Sun, Zhao-Li Hu, Ming Lu, Jian-Hua Ding, Gang Hu
Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson's disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6...
March 14, 2018: Cell Death & Disease
Zachary Curry, Jenny Wilkerson, Deniz Bagdas, Sarah Kyte, Nipa Patel, Giulia Donvito, Mohammed A Mustafa, Justin Poklis, Micah Niphakis, Ku-Lung Hsu, Benjamin F Cravatt, David A Gewirtz, M Imad Damaj, Aron H Lichtman
Although paclitaxel effectively treats various cancers, its debilitating peripheral neuropathic pain side effects often persist long after treatment has ended. Therefore, a compelling need exists for the identification of novel pharmacologic strategies to mitigate this condition. As inhibitors of monoacylglycerol lipase (MAGL), the primary hydrolytic enzyme of the endogenous cannabinoid 2-arachidonyolglycerol, produce antinociceptive effects in numerous rodent models of pain, we investigated whether inhibitors of this enzyme (i...
March 14, 2018: Journal of Pharmacology and Experimental Therapeutics
Tulika Mitra, Parash Prasad, Pritha Mukherjee, Susri Ray Chaudhuri, Urmi Chatterji, Sib S Roy
Ovarian cancer (OC) is the fourth most common gynecological malignancy due to its highly aggressive, recurrent, and drug-resistant nature. The last two features are rendered by the presence of cancer stem cells (CSCs). Factors like TGFβ1 and their downstream signaling pathways are upregulated in most cancers and are known to induce EMT and stemness, but the exact mechanisms underlying the process remain unelucidated. In our study, TGFβ1 induced enhanced stem-like properties like high expression of the pluripotent markers SOX2, OCT4a, and NANOG, along with CD44, and CD117 in the OC cells...
March 14, 2018: Journal of Cellular Biochemistry
Rong Wang, Lei Cao, Zhenxing Shen, Yongxiao Cao
Fine particle matters (PM2.5 ) is a well-known risk factor for cardiovascular diseases. However, the underlying molecular mechanisms are largely unknown. Vascular hyper-reactivity plays an important roles in the pathogenesis of cardiovascular diseases. The present study was designed to investigate a hypothesis that PM2.5 up-regulated endothelin receptors in mesenteric artery and the potential underlying mechanisms. Rat mesenteric arteries were cultured with PM2.5 . The artery contractile responses were recorded by a sensitive myograph...
March 13, 2018: Environmental Science and Pollution Research International
Simona Ceccarelli, Cristina Nodale, Enrica Vescarelli, Paola Pontecorvi, Valeria Manganelli, Giovanni Casella, Maria Giuseppina Onesti, Maurizio Sorice, Ferdinando Romano, Antonio Angeloni, Cinzia Marchese
Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells...
2018: Stem Cells International
Rong Wang, Danni Deng, Naiyuan Shao, Yuan Xu, Lian Xue, Ya Peng, Yatian Liu, Feng Zhi
Background: Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis. No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced. Therefore, developing new agents to treat GBM is important. Aim: This study aimed to evaluate the anti-tumor effect of evodiamine (Evo) on GBM cells, and to determine the underlying mechanisms involved...
2018: OncoTargets and Therapy
Min Hu, Yuehui Zhang, Jiaxing Feng, Xue Xu, Jiao Zhang, Wei Zhao, Xiaozhu Guo, Juan Li, Edvin Vestin, Peng Cui, Xin Li, Xiaoke Wu, Mats Brannstrom, Linus R Shao, Hakan Billig
Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance...
March 13, 2018: Journal of Endocrinology
Haiting Chen, Huifang Wang, Jianbin An, Qingli Shang, Jingxue Ma
BACKGROUND: This study aimed to explore the effects of plumbagin (PLB) on ARPE-19 cells and underlying mechanism. METHODS: Cultured ARPE-19 cells were treated with various concentrations (0, 5, 15, and 25 μM) of PLB for 24 h or with 15 μM PLB for 12, 24 and 48 h. Then cell viability was evaluated by MTT assay and DAPI staining, while apoptosis and cell cycle progression of ARPE cells were assessed by flow cytometric analysis. Furthermore, the level of main regulatory proteins was examinated by Western boltting and the expression of relative mRNA was tested by Real-Time PCR...
March 13, 2018: BMC Complementary and Alternative Medicine
Cui Zhang, Liang Li, Yuanda Jiang, Cuicui Wang, Baoming Geng, Yanqiu Wang, Jianling Chen, Fei Liu, Peng Qiu, Guangjie Zhai, Ping Chen, Renfu Quan, Jinfu Wang
Bone formation is linked with osteogenic differentiation of mesenchymal stem cells (MSCs) in the bone marrow. Microgravity in spaceflight is known to reduce bone formation. In this study, we used a real microgravity environment of the SJ-10 Recoverable Scientific Satellite to examine the effects of space microgravity on the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). hMSCs were induced toward osteogenic differentiation for 2 and 7 d in a cell culture device mounted on the SJ-10 Satellite...
March 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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