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p38 MAPK AP-1

Tong Wang, Xiaoxia Jin, Yingjun Liao, Qi Sun, Chaohong Luo, Gaoyang Wang, Fenghong Zhao, Yaping Jin
Subacute poisoning of 1,2-dichloroethane (1,2-DCE) has become a serious occupational problem in China, and brain edema is its main pathological consequence, but little is known about the underlying mechanisms. As the metabolite of 1,2-DCE, 2-chloroethanol (2-CE) is more reactive, and might play an important role in the toxic effects of 1,2-DCE. In our previous studies, we found that matrix metalloproteinases-9 (MMP-9) expression was enhanced in mouse brains upon treatment with 1,2-DCE, and in rat astrocytes exposed to 2-CE...
August 7, 2018: Cells
Xiaoxia Jin, Yingjun Liao, Xiaoqiong Tan, Jingjing Guo, Gaoyang Wang, Fenghong Zhao, Yaping Jin
Accumulated data have revealed that subacute poisoning of 1,2-dichloroethane (1,2-DCE), an industrial solvent used in some countries can cause encephalopathy, in which brain edema is the main pathological change. However, the underlying mechanisms are unclear. In the present study, we hypothesized that the p38 MAPK (p38) signaling pathway could be activated in 1,2-DCE-intoxicated mice, which in turn stimulates transcription factors, such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), and then enhances the expression of proinflammatory factors, including matrix metalloproteinase-9 (MMP-9), finally leading to blood-brain barrier (BBB) disruption and brain edema formation...
August 3, 2018: Neurotoxicology
Showgy Y Ma'ayeh, Livia Knörr, Karin Sköld, Alexandra Granham, Brendan R E Ansell, Aaron R Jex, Staffan G Svärd
Giardia intestinalis is a parasitic protist that causes diarrhea in humans, affecting mainly children of the developing world, elderly and immunocompromised individuals. Humans are infected by two major Giardia assemblages (i.e. genetic subtypes), A and B, with the latter being the most common. So far, there is little information on molecular or cellular changes during infections with assemblage B. Here, we used RNA sequencing to study transcriptional changes in Caco-2 intestinal epithelial cells (IECs) co-incubated with assemblage B (GS isolate) trophozoites for 1...
2018: Frontiers in Cellular and Infection Microbiology
Nitin A Das, Andrea J Carpenter, Tadashi Yoshida, Senthil A Kumar, Sandeep Gautam, Ricardo Mostany, Reza Izadpanah, Ashok Kumar, Srinivas Mummidi, Ulrich Siebenlist, Bysani Chandrasekar
Persistent inflammation promotes development and progression of heart failure (HF). TWEAK (TNF-Related WEAK Inducer Of Apoptosis), a NF-κB- and/or AP-1-responsive proinflammatory cytokine that signals via TWEAK receptor (TWEAKR), is expressed at high levels in human and preclinical models of HF. Since the adapter molecule TRAF3IP2 (TRAF3 Interacting Protein 2) is an upstream regulator of various proinflammatory pathways, including those activated by NF-κB and AP-1, we hypothesized that targeting TRAF3IP2 inhibits TWEAK-induced proinflammatory and pro-fibrotic responses in vitro and in vivo...
July 5, 2018: Journal of Molecular and Cellular Cardiology
Huatuo Zhu, Shujun Huang, Min Yue, Wenguo Chen, Chao Lu, Xinhe Lou, Chunxiao Li, Guodong Shan, Hongtan Chen, Xiaowei Xu, Guoqiang Xu, Lihua Chen
BACKGROUND: Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. AIM: The present study aimed to validate the underlying mechanism of UPF1 in UC. METHODS: UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice...
June 29, 2018: Digestive Diseases and Sciences
Ran Ma, Fang Yuan, Shaoxuan Wang, Yingping Liu, Tingting Fan, Fulai Wang
Acute pancreatitis (AP) is a common acute abdominal disease accompanied by systemic inflammatory response syndrome, and could even be complicated by multiple-organ damage. This study aimed to examine whether calycosin, an isoflavone isolated from Radix astragali with antioxidant and anti-inflammatory activity, could protect against AP induced by cerulein. To this end, Balb/C mice were injected with cerulein (50 μg/kg) to establish the animal model of AP. Calycosin (25 and 50 mg/kg, p.o.) was administered 1 h prior to the first cerulein injection...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Li Li, Lin Cai, Linxin Zheng, Yujie Hu, Weifeng Yuan, Zhenhui Guo, Weifeng Li
Pulmonary fibrosis (PF) is a life-threatening interstitial lung disease. In this study, we tried to reveal the model of action between high-mobility group box 1 (HMGB1) and α -smooth muscle actin ( α -SMA) and the protective role of gefitinib in pulmonary fibrosis induced by the administration of bleomycin aerosol in mice. For the mechanism study, lung tissues were harvested two weeks after modeling to detect the coexpression of HMGB1 and α -SMA by immunohistochemistry and immunofluorescence staining. Protein-DNA interactions were analyzed using a pulldown assay to study the relationship between HMGB1 and α -SMA...
2018: Oxidative Medicine and Cellular Longevity
Jing Wang, Fang He, Lingqiang Chen, Qin Li, Song Jin, Hongmei Zheng, Jun Lin, Hong Zhang, Sha Ma, Jian Mei, Juan Yu
OBJECTIVE: To explore the molecular mechanism of Res in regulation of pulmonary fibrosis (PF). METHODS: Rats were injected with bleomycin (BLM) to establish a PF model and treated with resveratrol (Res) and/or miR-21 agomir. After 14 days, lung tissues were collected for Hematoxylin-eosin and Masson's staining, and real-time quantitative polymerase chain reaction and Western blot were performed to detect fibrosis-related protein expression and the activation of the TGF-β1/Smad pathway...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yun Yao, Kehai Liu, Yueliang Zhao, Xiaoqian Hu, Mingfu Wang
Pterostilbene (Pte) and 4′-Methoxyresveratrol (4MR) are methylated derivatives of resveratrol. We investigated the anti-inflammatory effect of Pte and 4MR in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. Both Pte and 4MR significantly reduced LPS-induced nitric oxide release by inhibiting the inducible nitric oxide synthase mRNA expression. Moreover, both of them inhibited LPS-induced mRNA expression of inflammatory cytokines including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6 and IL-1β, and tumor necrosis factor α (TNF-α), and attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing p65 phosphorylation...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hyowon Choi, Weera Chaiyamongkol, Alexandra C Doolittle, Zariel I Johnson, Shilpa S Gogate, Zachary R Schoepflin, Irving M Shapiro, Makarand V Risbud
The nucleus pulposus (NP) of intervertebral discs experiences dynamic changes in tissue osmolarity because of diurnal loading of the spine. TonEBP/NFAT5 is a transcription factor that is critical in osmoregulation as well as survival of NP cells in the hyperosmotic milieu. The goal of this study was to investigate whether cyclooxygenase-2 (COX-2) expression is osmoresponsive and dependent on TonEBP, and whether it serves an osmoprotective role. NP cells up-regulated COX-2 expression in hyperosmotic media. The induction of COX-2 depended on elevation of intracellular calcium levels and p38 MAPK pathway, but independent of calcineurin signaling as well as MEK/ERK and JNK pathways...
June 8, 2018: Journal of Biological Chemistry
Miaomiao Yuan, Wei Meng, Wenzhen Liao, Sen Lian
Andrographis paniculata Nees is used as a functional food in Japan, Korea, India, and China. Andrographolide, a naturally occurring phytochemical identified in Andrographis paniculata, has been discovered to present anti-inflammatory and anticancer activities. Highly expressed interleukin (IL-8) has been detected in colorectal cancer and is implicated in angiogenesis. However, the effect and molecular mechanisms of IL-8 expression by andrographolide remain obscure in human colorectal cancer cells. The present study was aimed to investigate the effects of andrographolide on TNF-α-induced IL-8 expression and its underlying mechanisms...
May 23, 2018: Journal of Agricultural and Food Chemistry
Mrinalini Singh, Seema Yadav, Meetul Kumar, Shweta Saxena, Deepika Saraswat, Anju Bansal, Shashi B Singh
This study reports the role of MAPKs (JNK, ERK, and p38), and activator protein-1 (AP-1) transcription factor in the hypobaric hypoxia induced change in lung tissue. Healthy male Sprague-Dawley rats were exposed to hypobaric hypoxia for 6, 12, 24, 48, 72, and 120 hr. Hypoxia resulted in significant increase in reactive oxygen species (ROS), vascular endothelial growth factor (VEGF) and decreased nitric oxide (NO), these act as signaling molecules for activation of MAPK and also contribute in development of vascular leakage (an indicator of pulmonary edema) as confirmed by histological studies...
October 2018: Journal of Cellular Physiology
Myoung-Sook Shin, Ji Hoon Song, Pilju Choi, Jong Hun Lee, Song-Yi Kim, Kwang-Soon Shin, Jungyeob Ham, Ki Sung Kang
Panax ginseng Meyer has been used for the treatment of immune diseases and for strengthening the immune function. In this study, we evaluated the innate immune-stimulating functions and action mechanisms of white ginseng (WG) and heat-processed ginseng (HPG) in RAW264.7 cells. According to LC-MS analysis results, WG contained typical ginsenosides, such as Rb1, Rc, Rb2, Rd, and Rg1, whereas HPG contained Rg3, Rk1, and Rg5 as well as typical ginsenosides. HPG, not WG, enhanced NF-κB transcriptional activity, cytokine production (IL-6 and TNF-α), and MHC class I and II expression in RAW264...
May 9, 2018: Journal of Agricultural and Food Chemistry
Miao-Miao Zhou, Wen-Yan Zhang, Rui-Jun Li, Chao Guo, Shan-Shan Wei, Xiao-Meng Tian, Jun Luo, Ling-Yi Kong
BACKGROUND: Immunocytes-involved inflammation is considered to modulate the damage in various diseases. Herein, novel therapeutics suppressing over-activation of immunocytes could prove an effective strategy to prevent inflammation-related diseases. PURPOSE: The objective of this study is to evaluate the anti-inflammatory activity of Khayandirobilide A (KLA), a new andirobin-type limonoid with modified furan ring isolated from the Khaya senegalensis (Desr.) A. Juss...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Yiu To Yeung, Faisal Aziz, Angelica Guerrero-Castilla, Sandro Arguelles
During the past decade, an abundance of new evidence highlighted the importance of inflammation in the development of chronic pathologies such as neurodegeneration, cancer, diabetes, cardiovascular disease and inflammatory bowel disease. However, most of the current therapies do not address the underlying problem and better therapies are urgently needed. A growing number of researchers have discovered various signaling pathways that are associated with the initiation and progression of inflammation. Among different pathways, we will focus on three classical inflammatory pathways: p38 MAPK, IL-6/JAK/STAT3 and PI3K; and a non-classical inflammatory pathway, the Hippo...
2018: Current Pharmaceutical Design
Ji-Chun Ge, Xue-Qiang Zha, Chun-Yan Nie, Nian-Jun Yu, Qiang-Ming Li, Dai-Yin Peng, Jun Duan, Li-Hua Pan, Jian-Ping Luo
The present work investigated the inhibitory activity of the polysaccharide from cultivated Dendrobium huoshanense (cDHP) on lung inflammation in cigarette smoke (CS)-induced mouse model. cDHP was mainly composed of mannose and glucose in a molar ratio of 1.89: 1.00, and had a backbone with linkages of 1,4-Manp, 1,4-Glcp, 1,4,6-Manp and 1-Glcp. Hematoxylin and Eosin (HE) staining and immunohistochemistry analysis showed that cDHP can increase alveolar number, thicken alveolar wall, inhibit pulmonary bulla formation and decrease inflammatory cell infiltration as compared to the model group...
June 1, 2018: Carbohydrate Polymers
Pallavi Gurung, Suhrid Banskota, Nikita Katila, Jaya Gautam, Tara Man Kadayat, Dong-Young Choi, Eung Seok Lee, Tae Cheon Jeong, Jung-Ae Kim
The pathogenesis of inflammatory bowel disease (IBD) is associated with production of immense pro-inflammatory cytokines including TNF-α. Once generated, TNF-α stimulates production of various pro-inflammatory cytokines and disrupts mucosal barrier by inducing inflamed mucosal epithelial cell death. In the present study, we investigated inhibitory effects of TI-1-162, a hydroxyindenone derivative, against TNF-α-induced and TNBS-induced colon inflammation. TI-1-162 showed inhibitory effect on the TNF-α-induced adhesion of U937 monocytic cells to HT-29 colonic epithelial cells (IC50 = 0...
May 15, 2018: European Journal of Pharmacology
Xiao-Jing Wu, Hui-Min Liu, Xue-Min Song, Bo Zhao, Yan Leng, E-You Wang, Li-Ying Zhan, Qing-Tao Meng, Zhong-Yuan Xia
Blunt chest trauma with hemorrhagic shock (THS) frequently induces pulmonary inflammation that leads to acute lung injury (ALI). Penehyclidine hydrochloride (PHC) possesses anti‑inflammatory properties that may attenuate the systemic inflammatory response. The present study aimed to evaluate the molecular mechanism of PHC in modifying THS‑induced ALI in rats. Rats underwent either THS or a sham procedure. At 6 h subsequent to blunt chest trauma, arterial blood was drawn for blood gas and pro‑inflammatory factors analyses, and lung tissue samples were collected to examine pulmonary histopathological alterations, the wet/dry weight ratio, myeloperoxidase activity, and the protein expression levels of Toll-like receptor 4 (TLR4), phosphorylated (p‑)p38 mitogen‑activated protein kinase (MAPK), nuclear factor (NF)‑κB and activator protein‑1 (AP‑1)...
May 2018: Molecular Medicine Reports
Heewon Lee, Kyunglim Lee
Background: Histamine releasing factor (HRF) is a unique cytokine known to regulate a variety of immune cells in late allergic reactions. In the previous study, we revealed that the biologically active form of HRF is the dimerized translationally controlled tumor protein (dTCTP) for the first time, and confirmed the secretion of IL-8 cytokine by dTCTP in human bronchial epithelial cells. However, the signaling pathway by which dTCTP promotes the secretion of IL-8 is not known. Results: When the cells were stimulated with dTCTP, the canonical NF-κB pathway and ERK, JNK and p38 MAPK become activated...
2018: Cell & Bioscience
Xin Sun, Tao Zhang, Qifei Deng, Qirui Zhou, Xianchao Sun, Enlai Li, Dexin Yu, Caiyun Zhong
Benzidine, a known carcinogen, is closely associated with the development of bladder cancer (BC). Epithelial-mesenchymal transition (EMT) is a critical pathophysiological process in BC progression. The underlying molecular mechanisms of mitogen-activated protein kinase (MAPK) pathway, especially extracellular regulated protein kinases 5 (ERK5), in regulating benzidine-induced EMT remains unclarified. Hence, two human bladder cell lines, T24 and EJ, were utilized in our study. Briefly, cell migration was assessed by wound healing assay, and cell invasion was determined by Transwell assay...
March 31, 2018: Molecules and Cells
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