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Total 1410 results found since Jan 2013.

Crosstalk between TLR4-MyD88-NFκB and SCAP-SREBP2 pathways mediates macrophage foam cell formation.
This study was designed to investigate crosstalk between TLR4-MyD88-NFκB and SCAP-SREBP2 pathways in macrophage foam cell formation. Phorbol, 12-myristate, 13-acetate (PMA) activated-THP-1 macrophages were transfected with negative control or MyD88 siRNA. The transfected cells were incubated with LPS in the absence or presence of LDL or IKK inhibitor (BMS-345541). Intracellular cholesterol content was assessed. The mRNA and protein expression of LDLr, HMGCoAR, SCAP and SREBP2 were examined by real-time RT-PCR and Western blotting. The intracellular translocation of SCAP in the organelles was detected by immunofluorecence ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 18, 2013 Category: Physiology Authors: Li LC, Varghese Z, Moorhead JF, Lee CT, Chen JB, Ruan XZ Tags: Am J Physiol Heart Circ Physiol Source Type: research

ERK1/2 activation mediated by the nutlin‑3‑induced mitochondrial translocation of p53.
In this study, we propose a novel mechanism involved in the p53-induced MAPK activation. Nutlin-3 induced the phosphorylation of EGFR, MAPK/ERK kinase (MEK)1/2 and extracellular signal-regulated kinase (ERK)1/2 in U2OS human osteosarcoma cells harboring wild-type p53. This phosphorylation was completely inhibited by p53 siRNA, but not by pifithrin (PFT)-α, an inhibitor of the trans-criptional activity of p53. While the nutlin-3-induced EGFR phosphorylation was prevented by the inactivation of ERK1/2, the nutlin-3-induced MEK1/2-ERK1/2 phosphorylation was still observed in the cell...
Source: International Journal of Oncology - January 31, 2013 Category: Cancer & Oncology Authors: Lee SY, Shin SJ, Kim HS Tags: Int J Oncol Source Type: research

MARCKS and HSP70 interactions regulate mucin secretion by human airway epithelial cells in vitro.
Abstract MARCKS (myristoylated alanine-rich C kinase substrate) protein has been recognized as a key regulatory molecule controlling mucin secretion by airway epithelial cells in vitro and in vivo. We recently showed that two intracellular chaperones, heat shock protein 70 (HSP70) and cysteine string protein (CSP), associate with MARCKS in the secretory mechanism. To elucidate more fully MARCKS-HSP70 interactions in this process, studies were performed in well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture utilizing specific pharmacological inhibition of HS...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - February 1, 2013 Category: Cytology Authors: Fang S, Crews AL, Chen W, Park J, Yin Q, Ren XR, Adler KB Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Nicotine-induced epithelial-mesenchymal transition via Wnt/{beta}-catenin signaling in human airway epithelial cells
Epithelial-mesenchymal transition (EMT) has been proposed to be a mechanism in airway remodeling, which is a characteristic of chronic obstructive pulmonary disease (COPD). Studies have shown that cigarette smoke and nicotine are factors that induce Wnt/β-catenin activation, which is a pathway that has also been implicated in EMT. The main aim of this study was to test whether human bronchial epithelial cells are able to undergo EMT in vitro following nicotine stimulation via the Wnt3a/β-catenin signaling pathway. We show that nicotine activates the Wnt3a signal pathway, which leads to the translocation of β...
Source: AJP: Lung Cellular and Molecular Physiology - February 15, 2013 Category: Respiratory Medicine Authors: Zou, W., Zou, Y., Zhao, Z., Li, B., Ran, P. Tags: CALL FOR PAPERS Source Type: research

Klebsiella pneumoniae targets an EGF receptor‐dependent pathway to subvert inflammation
Summary The NF‐κB transcriptional factor plays a key role governing the activation of immune responses. Klebsiella pneumoniae is an important cause of community‐acquired and nosocomial pneumonia. Evidence indicates that K. pneumoniae infections are characterized by lacking an early inflammatory response. Recently, we have demonstrated that Klebsiella antagonizes the activation of NF‐κB via the deubiquitinase CYLD. In this work, by applying a high‐throughput siRNA gain‐of‐function screen interrogating the human kinome, we identified 17 kinases that when targeted by siRNA restored IL‐1β‐dependent NF‐κ...
Source: Cellular Microbiology - February 17, 2013 Category: Microbiology Authors: Christian G. Frank, Verónica Reguerio, Marion Rother, David Moranta, André P. Maeurer, Junkal Garmendia, Thomas F. Meyer, José A. Bengoechea Tags: Research Article Source Type: research

Role of p21WAF1 in IL-20-induced Migration Cell Biology
The role of inflammatory cytokine interleukin-20 (IL-20) has not yet been studied in cancer biology. Here, we demonstrated up-regulation of both IL-20 and IL-20R1 in muscle-invasive bladder cancer patients. The expressions of IL-20 and IL-20R1 were observed in bladder cancer 5637 and T-24 cells. We found that IL-20 significantly increased the expression of matrix metalloproteinase (MMP)-9 via binding activity of NF-κB and AP-1 in bladder cancer cells and stimulated the activation of ERK1/2, JNK, p38 MAPK, and JAK-STAT signaling. Among the pathways examined, only ERK1/2 inhibitor U0126 significantly inhibited IL-20-induced...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Lee, S.-J., Cho, S.-C., Lee, E.-J., Kim, S., Lee, S.-B., Lim, J.-H., Choi, Y. H., Kim, W.-J., Moon, S.-K. Tags: Immunology Source Type: research

MARCKS and HSP70 interactions regulate mucin secretion by human airway epithelial cells in vitro
Myristoylated alanine-rich C kinase substrate (MARCKS) protein has been recognized as a key regulatory molecule controlling mucin secretion by airway epithelial cells in vitro and in vivo. We recently showed that two intracellular chaperones, heat shock protein 70 (HSP70) and cysteine string protein (CSP), associate with MARCKS in the secretory mechanism. To elucidate more fully MARCKS-HSP70 interactions in this process, studies were performed in well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture utilizing specific pharmacological inhibition of HSP70 with pyrimidin...
Source: AJP: Lung Cellular and Molecular Physiology - April 15, 2013 Category: Respiratory Medicine Authors: Fang, S., Crews, A. L., Chen, W., Park, J., Yin, Q., Ren, X.-R., Adler, K. B. Tags: ARTICLES Source Type: research

Suppression of TRPC6 Expression by NF-{kappa}B Cell Biology
This study was carried out to explore the molecular mechanism for down-regulation of TRPC6 expression in the reactive oxygen species (ROS)/PKC signaling in kidney cells. In cultured human mesangial cells, H2O2 and TNF-α inhibited TRPC6 mRNA expression in a time-dependent manner. Inhibition of NF-κB reversed both H2O2- and phorbol 12-myristate 13-acetate (PMA)-induced decrease in TRPC6 protein expression. Activation of NF-κB by knocking down IκBα using siRNA could mimic the suppressive effect of ROS/PKC on TRPC6. a Ca2+ imaging study showed that activation and inhibition of NF-κB significantly decreased and increased ...
Source: Journal of Biological Chemistry - May 3, 2013 Category: Chemistry Authors: Wang, Y., Ding, M., Chaudhari, S., Ding, Y., Yuan, J., Stankowska, D., He, S., Krishnamoorthy, R., Cunningham, J. T., Ma, R. Tags: Signal Transduction Source Type: research

Cell signalling
Conclusions: Taken together, it is likely that klotho protects against renal fibrotic process accompanied by down-regulation of fibrotic markers, counteracting to TGF-β, and one of possible mechanism mediating translocation of Na/K ATPase, resulting in Ca+ channel stabilization/alternation of Ca+ ion concentration. Klotho should be involved in the accentuation of the progression of renal fibrosis in CKD.
Source: Nephrology Dialysis Transplantation - May 10, 2013 Category: Urology & Nephrology Authors: Tsuchiya, K., Shiohira, S., Sugiura, H., Suzuki, M., Okano, K., Nitta, K., Kaesler, N., Immendorf, S., Ouyang, C., Carmeliet, P., Floege, J., Kruger, T., Schlieper, G., Georgescu, A., Kalucka, J., Olbrich, S., Baumgartl, J., Hackenbeck, T., Eckardt, K.-U. Tags: Abstracts Source Type: research

TRAIL regulates collagen production through HSF1-dependent Hsp47 expression in activated hepatic stellate cells.
In this study, we showed that TRAIL treatment inhibited Hsp47 expression in dose- and time-dependent manners, subsequently leading to the decrease of collagen production in activated human hepatic stellate LX-2 cells. Overexpression of Hsp47 in LX-2 cells acquired resistance for TRAIL-induced collagen reduction and conversely, siRNA suppression of Hsp47 enhanced the decrease of collagen production due to TRAIL treatment. Moreover, we found that Hsp47 expression was under the transcriptional control of heat shock factor (HSF) 1 which is highly located on nucleus in activated human hepatic stellate LX-2 cells. Treatment of L...
Source: Cellular Signalling - April 12, 2013 Category: Cytology Authors: Park SJ, Sohn HY, Park SI Tags: Cell Signal Source Type: research

The role of intracellular high-mobility group box 1 in the early activation of Kupffer cells and the development of Con A-induced acute liver failure.
Abstract Acute liver failure (ALF) is a highly complex syndrome characterized by devastating activation of early activation of Kupffer cells (KCs) has been implicated in the pathogenesis of ALF. However, the factors regulating KC early activation are virtually unexplored. The aim of present study was to determine the role of the intracellular high-mobility group box 1 (HMGB1) in modulating the early activation of KCs during ALF. The intravenous injection of Concanavalin A (Con A) was used to establish a mouse model of ALF. The dynamic pro-inflammatory properties and MHC II expression of KCs were measured by qRT-PC...
Source: Immunobiology - April 27, 2013 Category: Allergy & Immunology Authors: Yang Q, Liu Y, Shi Y, Zheng M, He J, Chen Z Tags: Immunobiology Source Type: research

The in vitro apoptotic effects of A248 and A1659, newly synthetic HDAC inhibitors in oral cancer cells
ConclusionThese results suggest that A248 and A1659, two new HDAC inhibitors may be attractive therapeutic drug candidates for targeting Sp1 in human oral cancer cells.This article is protected by copyright. All rights reserved.
Source: Oral Diseases - July 1, 2013 Category: ENT & OMF Authors: Ji‐Ae Shin, Gyoonhee Han, Song‐Kyu Park, Kiho Lee, Hyun‐Jung Kim, Sung‐Dae Cho, Hwan Mook Kim Tags: Original Article Source Type: research

The in vitro apoptotic effects of A248 and A1659, newly synthetic histone deacetylase inhibitors in oral cancer cells
ConclusionThese results suggest that A248 and A1659, two new HDAC inhibitors, may be attractive therapeutic drug candidates for targeting Sp1 in human oral cancer cells.
Source: Oral Diseases - July 14, 2013 Category: ENT & OMF Authors: J‐A Shin, G Han, S‐K Park, K Lee, H‐J Kim, S‐D Cho, HM Kim Tags: Original Article Source Type: research

CaMK II/CREB/Wnt/{beta}-Catenin Signaling in Podocyte In{jnodot}ury Cell Biology
In this study, we found that Ang II induced Wnt1 expression and β-catenin nuclear translocation in cultured mouse podocytes. Blocking Wnt signaling with Dickkopf-1 (Dkk1) or β-catenin siRNA attenuated Ang II-induced podocyte injury. Ang II could also induce the phosphorylation of calmodulin-dependent protein kinase (CaMK) II and cAMP response element-binding protein (CREB) in cultured podocytes. Blockade of this pathway with CK59 or CREB siRNA could significantly inhibit Ang II-induced Wnt/β-catenin signaling and podocyte injury. In in vivo studies, administration of Ang II promoted Wnt/β-catenin signaling, aggregated ...
Source: Journal of Biological Chemistry - August 9, 2013 Category: Chemistry Authors: Jiang, L., Xu, L., Song, Y., Li, J., Mao, J., Zhao, A. Z., He, W., Yang, J., Dai, C. Tags: Signal Transduction Source Type: research

In silico analysis and experimental validation of molecular mechanisms of salvianolic acid A‐inhibited LPS‐stimulated inflammation, in RAW264.7 macrophages
ConclusionsIn silico analysis and experimental validation together demonstrated that SAA exhibited its anti‐inflammatory effect via the p38‐HO‐1 pathway in LPS‐stimulated RAW264.7 cells, reduced transfer of NF‐κB to the nuclei and thus reduced production of inflammatory mediators.
Source: Cell Proliferation - August 24, 2013 Category: Cytology Authors: J. Huang, Y. Qin, B. Liu, G. Y. Li, L. Ouyang, J. H. Wang Tags: Original Article Source Type: research