oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2019 ( 121 )

2018 ( 1046 )

2017 ( 1055 )

2016 ( 978 )

Custom range...

Search Results: 1 - 10 of 64743 matches for " Chuen-Mao Yang "
All listed articles are free for downloading (OA Articles)
Page 1 /64743
Display every page Item
Induction of heme oxygenase-1 attenuates lipopolysaccharide-induced cyclooxygenase-2 expression in mouse brain endothelial cells
Ruey-Horng Shih, Chuen-Mao Yang
Journal of Neuroinflammation , 2010, DOI: 10.1186/1742-2094-7-86
Abstract: The aim of the present study was to investigate whether the up-regulation of HO-1 regulates COX-2 expression induced by lipopolysaccharide (LPS), an endotoxin produced by Gram negative bacteria, in mouse brain endothelial cells (bEnd.3)Cultured bEnd.3 cells were used to investigate LPS-induced COX-2 expression and PGE2 production. Cobalt protoporphyrin IX (CoPP, an HO-1 inducer), infection with a recombinant adenovirus carried with HO-1 gene (Adv-HO-1), or zinc protoporphyrin (ZnPP, an HO-1 inhibitor) was used to stimulate HO-1 induction or inhibit HO-1 activity. The expressions of COX-2 and HO-1 were evaluated by western blotting. PGE2 levels were detected by an enzyme-linked immunoassay. Hemoglobin (a chelator of carbon monoxide, CO, one of metabolites of HO-1) and CO-RM2 (a CO releasing molecule) were used to investigate the mechanisms of HO-1 regulating COX-2 expression.We found that LPS-induced COX-2 expression and PGE2 production were mediated through NF-κB (p65) via activation of Toll-like receptor 4 (TLR4). LPS-induced COX-2 expression was inhibited by HO-1 induction by pretreatment with CoPP or infection with Adv-HO-1. This inhibitory effect of HO-1 was reversed by pretreatment with either ZnPP or hemoglobin. Pretreatment with CO-RM2 also inhibited TLR4/MyD88 complex formation, NF-κB (p65) activation, COX-2 expression, and PGE2 production induced by LPS.We show here a novel inhibition of HO-1 on LPS-induced COX-2/PGE2 production in bEnd.3. Our results reinforce the emerging role of cerebral endothelium-derived HO-1 as a protector against cerebral vascular inflammation triggered by bacterial infection.Sepsis is a life-threatening clinical syndrome which is correlated with a mortality of 30% [1]. During Gram negative sepsis, lipopolysaccharide (LPS), an endotoxin produced by Gram negative bacteria, stimulates various pro-inflammatory cytokines and mediators releasing [2]. For example, prostaglandin E2 (PGE2), an arachidonic acid metabolite synthesized by cycl
Inflammatory Signalings Involved in Airway and Pulmonary Diseases
I-Ta Lee,Chuen-Mao Yang
Mediators of Inflammation , 2013, DOI: 10.1155/2013/791231
Abstract:
Calmodulin kinase II-dependent transactivation of PDGF receptors mediates astrocytic MMP-9 expression and cell motility induced by lipoteichoic acid
Hui-Hsin Wang, Hsi-Lung Hsieh, Chuen-Mao Yang
Journal of Neuroinflammation , 2010, DOI: 10.1186/1742-2094-7-84
Abstract: The goal of this study was to examine whether LTA-induced cell migration is mediated by calcium/calmodulin (CaM)/CaM kinase II (CaMKII)-dependent transactivation of the PDGFR pathway in rat brain astrocytes (RBA-1 cells).Expression and activity of MMP-9 induced by LTA was evaluated by zymographic, western blotting, and RT-PCR analyses. MMP-9 regulatory signaling pathways were investigated by treatment with pharmacological inhibitors or using dominant negative mutants or short hairpin RNA (shRNA) transfection, and chromatin immunoprecipitation (ChIP)-PCR and promoter activity reporter assays. Finally, we determined the cell functional changes by cell migration assay.The data show that c-Jun/AP-1 mediates LTA-induced MMP-9 expression in RBA-1 cells. Next, we demonstrated that LTA induces MMP-9 expression via a calcium/CaM/CaMKII-dependent transactivation of PDGFR pathway. Transactivation of PDGFR led to activation of PI3K/Akt and JNK1/2 and then activated c-Jun/AP-1 signaling. Activated-c-Jun bound to the AP-1-binding site of the MMP-9 promoter, and thereby turned on transcription of MMP-9. Eventually, up-regulation of MMP-9 by LTA enhanced cell migration of astrocytes.These results demonstrate that in RBA-1 cells, activation of c-Jun/AP-1 by a CaMKII-dependent PI3K/Akt-JNK activation mediated through transactivation of PDGFR is essential for up-regulation of MMP-9 and cell migration induced by LTA. Understanding the regulatory mechanisms underlying LTA-induced MMP-9 expression and functional changes in astrocytes may provide a new therapeutic strategy for Gram-positive bacterial infections in brain disorders.Bacterial infections are responsible for a number of inflammatory diseases including brain inflammation [1]. Gram-positive bacterial infections of the central nervous system (CNS) occur either as bacterial meningitis or as brain abscess, being localized to the membranes surrounding the brain or in its parenchyma, respectively [2]. Lipoteichoic acid (LTA), an amph
Intracellular Signaling Mechanisms Underlying the Expression of Pro-inflammatory Mediators in Airway Diseases
Chuen-Mao Yang,Hsi-Lung Hsieh,Chiang-Wen Lee
Chang Gung Medical Journal , 2005,
Abstract: asthma and airway inflammation mechanisms. Elevated levels of proinflammatorycytokines including tumor necrosis factor-α and interleukin-1β in the bronchoalveolar lavage fluid have been detected inasthmatic patients. Cytokines exert as potent stimuli in inflammatoryresponses through up-regulation of many gene expressions, includingcytokines, chemokines, cytosolic phospholipase A2, cyclooxygenase,adhesion molecules and matrix metalloproteinases. The extent of thesegene expressions is correlated with the severity of inflammation.However, the intracellular signaling mechanisms underlying theexpression of target proteins regulated by these factors are elusive. Themechanisms underlying actions by cytokines may be integrated to thesignaling networks that augment airway inflammation by recruitingleukocytes and leading to airway remodeling. Although cytokines havebeen reported to activate mitogen-activated protein kinases includingp42/p44 and p38, and c-Jun N-terminal kinase, the relationship between the activation ofthese pathways and expression of inflammatory genes remains unknown. Moreover, manygenes regulated by mitogen-activated protein kinases are dependent on NF-κB for transcription.NF-κB has also been shown to be involved in target protein expression at the transcriptionallevel in various cell types. We review the mechanisms underlying the intracellular signalinginvolved in several target protein expressions induced by cytokines in airway residentcells. Conclusion: Increased understanding of signal transduction mechanisms underlyingtarget protein gene expression will create opportunities for the development of anti-inflammationtherapeutic strategies
c-Src-dependent EGF receptor transactivation contributes to ET-1-induced COX-2 expression in brain microvascular endothelial cells
Hsi-Lung Hsieh, Chin-Chung Lin, Hui-Ju Chan, Caleb M Yang, Chuen-Mao Yang
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-152
Abstract: The goal of this study was to examine whether ET-1-induced COX-2 expression and prostaglandin E2 (PGE2) release were mediated through a c-Src-dependent transactivation of epidermal growth factor receptor (EGFR) pathway in brain microvascular endothelial cells (bEnd.3 cells).The expression of COX-2 induced by ET-1 was evaluated by Western blotting and RT-PCR analysis. The COX-2 regulatory signaling pathways were investigated by pretreatment with pharmacological inhibitors, short hairpin RNA (shRNA) or small interfering RNA (siRNA) transfection, chromatin immunoprecipitation (ChIP), and promoter activity reporter assays. Finally, we determined the PGE2 level as a marker of functional activity of COX-2 expression.First, the data showed that ET-1-induced COX-2 expression was mediated through a c-Src-dependent transactivation of EGFR/PI3K/Akt cascade. Next, we demonstrated that ET-1 stimulated activation (phosphorylation) of c-Src/EGFR/Akt/MAPKs (ERK1/2, p38 MAPK, and JNK1/2) and then activated the c-Jun/activator protein 1 (AP-1) via Gq/i protein-coupled ETB receptors. The activated c-Jun/AP-1 bound to its corresponding binding sites within COX-2 promoter, thereby turning on COX-2 gene transcription. Ultimately, upregulation of COX-2 by ET-1 promoted PGE2 biosynthesis and release in bEnd.3 cells.These results demonstrate that in bEnd.3 cells, c-Src-dependent transactivation of EGFR/PI3K/Akt and MAPKs linking to c-Jun/AP-1 cascade is essential for ET-1-induced COX-2 upregulation. Understanding the mechanisms of COX-2 expression and PGE2 release regulated by ET-1/ETB system on brain microvascular endothelial cells may provide rational therapeutic interventions for brain injury and inflammatory diseases.
Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells
I-Ta Lee, Ruey-Horng Shih, Chih-Chung Lin, Jung-Tsan Chen, Chuen-Mao Yang
Cell Communication and Signaling , 2012, DOI: 10.1186/1478-811x-10-33
Abstract: We demonstrated that LPS induced VCAM-1 mRNA and protein levels associated with an increase in the promoter activity of VCAM-1, determined by Western blot, RT-PCR, and promoter assay. LPS-induced responses were inhibited by transfection with siRNAs of TLR4, myeloid differentiation factor 88 (MyD88), Nox2, Nox4, p47phox, c-Src, p38 MAPK, activating transcription factor 2 (ATF2), and p300 or pretreatment with the inhibitors of reactive oxygen species (ROS, edaravone), NADPH oxidase [apocynin (APO) or diphenyleneiodonium chloride (DPI)], c-Src (PP1), p38 MAPK (SB202190), and p300 (GR343). LPS induced NADPH oxidase activation, ROS production, and p47phox translocation from the cytosol to the membrane, which were reduced by PP1 or c-Src siRNA. We observed that LPS induced TLR4, MyD88, c-Src, and p47phox complex formation determined by co-immunoprecipitation and Western blot. We further demonstrated that LPS stimulated ATF2 and p300 phosphorylation and complex formation via a c-Src/NADPH oxidase/ROS/p38 MAPK pathway. Up-regulation of VCAM-1 led to enhancing monocyte adhesion to HRMCs challenged with LPS, which was inhibited by siRNAs of c-Src, p47phox, p38 MAPK, ATF2, and p300 or pretreatment with an anti-VCAM-1 neutralizing antibody.In HRMCs, LPS-induced VCAM-1 expression was, at least in part, mediated through a TLR4/MyD88/ c-Src/NADPH oxidase/ROS/p38 MAPK-dependent p300 and ATF2 pathway associated with recruitment of monocyte adhesion to kidney. Blockade of these pathways may reduce monocyte adhesion via VCAM-1 suppression and attenuation of the inflammatory responses in renal diseases.Mesangial cells (MCs) response to various pathological stimuli associated with the main events of glomerular inflammation, including leukocyte infiltration, cell proliferation, and fibrosis, which were predominantly mediated through induction of adhesion molecules [1,2]. In bacteria-induced glomerulonephritis, lipopolysaccharide (LPS, a key component of the outer membranes of Gram-negati
NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes
Hsi-Lung Hsieh, Chih-Chung Lin, Ruey-Horng Shih, Li-Der Hsiao, Chuen-Mao Yang
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-110
Abstract: Herein we explored whether LTA-induced MMP-9 expression was mediated through redox signals in rat brain astrocytes (RBA-1 cells).Upregulation of MMP-9 by LTA was evaluated by zymographic and RT-PCR analyses. Next, the MMP-9 regulatory pathways were investigated by pretreatment with pharmacological inhibitors or transfection with small interfering RNAs (siRNAs), Western blotting, and chromatin immunoprecipitation (ChIP)-PCR and promoter activity reporter assays. Moreover, we determined the cell functional changes by migration assay.These results showed that LTA induced MMP-9 expression via a PKC(α)-dependent pathway. We further demonstrated that PKCα stimulated p47phox/NADPH oxidase 2 (Nox2)-dependent reactive oxygen species (ROS) generation and then activated the ATF2/AP-1 signals. The activated-ATF2 bound to the AP-1-binding site of MMP-9 promoter, and thereby turned on MMP-9 gene transcription. Additionally, the co-activator p300 also contributed to these responses. Functionally, LTA-induced MMP-9 expression enhanced astrocytic migration.These results demonstrated that in RBA-1 cells, activation of ATF2/AP-1 by the PKC(α)-mediated Nox(2)/ROS signals is essential for upregulation of MMP-9 and cell migration enhanced by LTA.Matrix metalloproteinases (MMPs) comprise a family of calcium- and zinc-dependent proteinases, and are involved in normal development and wound healing as well as in pathological conditions such as atherosclerosis and metastasis. In brain, MMP-9 has been shown to be upregulated during various CNS diseases [1,2]. Previous reports have indicated that a series of functional element-binding sites have been identified, including NF-κB, Ets and AP-1 within the MMP-9 promoter [3], which can be regulated by diverse stimuli. Moreover, proinflammatory factors including cytokines, endotoxins and oxidative stress have been reported to upregulate MMP-9 in astrocytes in vitro [4-6], implying that MMP-9 activity may be regulated by diverse factors in the CNS du
Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells
Ruey-Horng Shih, Shin-Ei Cheng, Li-Der Hsiao, Yu Kou, Chuen-Mao Yang
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-104
Abstract: The aim of the present study was to investigate the mechanisms underlying CS modulating HO-1 protein expression in cerebral endothelial cells.Cultured cerebral endothelial cells (bEnd.3) were used to investigate whether a particulate phase of cigarette smoke extract (PPCSE) regulates HO-1 expression and to investigate the molecular mechanisms involved in HO-1 expression in bEnd.3 cells.We demonstrated that PPCSE (30 μg/ml) significantly induced HO-1 protein expression and its enzymatic activity in bEnd.3 cells determined by western blotting and bilirubin formation, respectively. PPCSE-induced HO-1 expression was mediated through phosphatidylcholine phospholipase C (PC-PLC), PKCδ, and PI3K/Akt which were observed by pretreatment with their respective pharmacological inhibitors or transfection with dominant negative mutants of PKCδ and Akt. ROS scavenger (N-acetyl-L-cysteine, NAC) blocked the PPCSE-induced ROS generation and HO-1 expression. Pretreatment with selective inhibitors of PKCδ (rottlerin) and NADPH oxidase [diphenyleneiodonium chloride (DPI) and apocynin (APO)] attenuated the PPCSE-induced NADPH oxidase activity, ROS generation, and HO-1 expression. In addition, we found that PPCSE induced PI3K/Akt activation via NADPH oxidase/ROS-dependent PDGFR phosphorylation.Taken together, these results suggested that PPCSE-induced HO-1 expression is mediated by a PC-PLC/PKCδ/NADPH oxidase-dependent PDGFR/PI3K/Akt pathway in bEnd.3 cells.Cigarette smoke (CS) is a complex aerosol that can be separated into gas and particulate phases. Particulate phase of CS extract (PPCSE), such as lipophilic components, could pass the lipid bilayer of respiratory membranes [1] into blood stream. Therefore, the damage of CS not only limits to lung tissue but also vascular system. CS is a known risk factor not only for peripheral cardiovascular inflammation-related diseases [2,3] but also for cerebrovascular diseases, such as stroke [4].In the brain, the inducible form of heme oxygenase
Transforming growth factor-β1 induces matrix metalloproteinase-9 and cell migration in astrocytes: roles of ROS-dependent ERK- and JNK-NF-κB pathways
Hsi-Lung Hsieh, Hui-Hsin Wang, Wen-Bin Wu, Po-Ju Chu, Chuen-Mao Yang
Journal of Neuroinflammation , 2010, DOI: 10.1186/1742-2094-7-88
Abstract: Rat brain astrocytes (RBA-1) were used. MMP-9 expression was analyzed by gelatin zymography and RT-PCR. The involvement of signaling molecules including MAPKs and NF-κB in the responses was investigated using pharmacological inhibitors and dominant negative mutants, determined by western blot and gene promoter assay. The functional activity of MMP-9 was evaluated by cell migration assay.Here we report that TGF-β1 induces MMP-9 expression and enzymatic activity via a TGF-β receptor-activated reactive oxygen species (ROS)-dependent signaling pathway. ROS production leads to activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun-N-terminal kinase (JNK) and then activation of the NF-κB transcription factor. Activated NF-κB turns on transcription of the MMP-9 gene. The rat MMP-9 promoter, containing a NF-κB cis-binding site, was identified as a crucial domain linking to TGF-β1 action.Collectively, in RBA-1 cells, activation of ERK1/2- and JNK-NF-κB cascades by a ROS-dependent manner is essential for MMP-9 up-regulation/activation and cell migration induced by TGF-β1. These findings indicate a new regulatory pathway of TGF-β1 in regulating expression of MMP-9 in brain astrocytes, which is involved in physiological and pathological tissue remodeling of central nervous system.Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endopeptidases that play an important role in the turnover of extracellular matrix (ECM) and function in physiological and pathological processes [1]. In the central nervous system (CNS), MMPs, and MMP-9 especially, are implicated in development, morphogenesis, wounding healing, neurite outgrowth, and immune cell migration [2]. In addition, they also participate in the pathogenesis of several CNS diseases such as stroke, Alzheimer's disease, neuroinflammation, and malignant glioma [3]. Among members of the MMP family, MMP-9 has been shown to be elevated in various brain disorders [4-6]. Moreover, several pro-infla
NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes
Chih-Chung Lin, Hsi-Lung Hsieh, Ruey-Horng Shih, Pei-Ling Chi, Shin-Ei Cheng, Jin-Chung Chen, Chuen-Mao Yang
Cell Communication and Signaling , 2012, DOI: 10.1186/1478-811x-10-35
Abstract: In the study, we first demonstrated that reactive oxygen species (ROS) plays a crucial role in BK-induced MMP-9 expression in cultured brain astrocytes (in vitro) and animal brain tissue (in vivo) models. Next, BK-induced MMP-9 expression is mediated through a Ca2+-mediated PKC-α linking to p47phox/NADPH oxidase 2 (Nox2)/ROS signaling pathway. Nox2-dependent ROS generation led to activation and up-regulation of the downstream transcriptional factor AP-1 (i.e. c-Fos and c-Jun), which bound to MMP-9 promoter region, and thereby turned on transcription of MMP-9 gene. Functionally, BK-induced MMP-9 expression enhanced astrocytic migration.These results demonstrated that in RBA-1 cells, activation of AP-1 (c-Fos/c-Jun) by the PKC-α-mediated Nox2/ROS signals is essential for up-regulation of MMP-9 and cell migration enhanced by BK.Matrix metalloproteinases (MMPs) is a large family of zinc-dependent endopeptidases, which play an important role in the turnover of extracellular matrix (ECM) and pathophysiological processes [1]. In the central nervous system (CNS), MMPs, in particular MMP-9, have been shown to be involved in morphogenesis, wounding healing, and neurite outgrowth, [2]. Up-regulation of MMP-9 has been induced by various brain injuries, which may participate in the pathogenesis of brain diseases [3]. Moreover, cytokines and lipopolysaccharide (LPS) have been shown to induce MMP-9 expression and activity in culture rat brain astrocytes [4,5]. These studies demonstrated that MMP-9 may be involved in brain inflammation and injury.Reactive oxygen species (ROS) are produced by various enzymatic and chemical processes or directly inhaled, including O2-, ·OH, and hydrogen peroxide (H2O2). The ROS at low level have physiological roles as signaling molecules in various cellular and developmental processes [6,7] and killing of invading microorganisms [8]. In contrast, recent report indicated that oxidative stress plays an important role in the progression of various disea
Page 1 /64743
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.