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Source: European Respiratory Journal
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Total 64 results found since Jan 2013.

PDK1/RSK1-dependent C/EBP{beta} activation is involved in thrombin-induced expression of orosomucoid 1-like 3 (ORMDL3) and IL-8/CXCL8 in human lung epithelial cells
In this study, we investigated that the role of phosphoinositide-dependent kinase 1 (PDK1), ribosomal S6 kinase 1 (RSK1), and CCAAT/enhancer-binding protein β (C/EBPβ) in thrombin-induced expression of ORMDL3 and IL-8/CXCL8 in human lung epithelial cells (A549). We found that treatment of cells with thrombin caused ORMDL3 mRNA and protein expression. Thrombin-induced IL-8/CXCL8-luciferase activity or IL-8/CXCL8 release was inhibited by ORMDL3 siRNA, BX-912 (a PDK1 inhibitor), and PDK1 siRNA. Moreover, thrombin-stimulated ORMDL3 expression was attenuated by BX-912, PDK1 siRNA, RSK1 siRNA, and C/EBPβ siRNA. Th...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Chen, B.-C., Huang, M.-F. Tags: Airway Pharmacology and Treatment Source Type: research

Late-breaking abstract: EGFR specific single chain antibody deliver siRNAs restore gefitinib sensitivity in resistant NSCLC cells
To overcome TKIs resistance, we developed scFv and s-9R, two human single chain antibodies against EGFR(fig.1A). Here, we showed s-9R could deliver FAM-siRNA into EGFR positve NSCLC cells(fig.1B). A549, H1993 and H1975 were either transfected with KRAS, MET or EGFR siRNA or co-incubated with scFv/s-9R/ indicated siRNA mixtures, following treated with gefitinib. Compared with the control groups, the target genes' expression level were down-regulated in the s-9R/siRNA mixture groups detected by RT-qPCR and western blot(fig.1C and D). In vivo, s-9R/siRNA mixtures restored gefitinib sensitivity in TKIs resistance cells measure...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Lu, Y., Liu, L., Zhang, R., Ren, X. Tags: 11.1 Lung Cancer Source Type: research

The effects of INTS12 knockdown on processing of snRNAs
Conclusions: INTS12 is likely to play an important role in HBEC function via snRNA processing: this may affect transcription globally.Funding: Medical Research Council1. Baillat et al. (2005) Cell 123 (2): 265–76.2. Obeidat et al. (2013) PLoSOne 18;8(9): e74630.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Kheirallah, A. K., Hodge, E., Nelson, C., Sayers, I., Hall, I. Tags: 3.2 Airway Cell Biology and Immunopathology Source Type: research

LSC 2014 abstract - ROR{gamma} t-specific RNAi decreases allergic airway inflammation and airway hyperresponsiveness in a mouse model of neutrophilic asthma
Conclusion: Our data show that knockdown of ROR t by gene silencing improved airway inflammation in a mouse model of experimental asthma and may have therapeutic potential for the treatment of neutrophilic asthma.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Webering, S., Lunding, L., Fehrenbach, H., Wegmann, M. Tags: 5.3 Allergy and Immunology Source Type: research

INTS12 knockdown leads to perturbation of genes and pathways of relevance to airway biology
Conclusions: INTS12 regulates pathways important in lung function through perturbation of genes belonging to e.g. collagen formation pathway. INTS12 is likely to control protein synthesis through effects on tRNA aminoacylation pathway.Funding: Medical Research Council.
Source: European Respiratory Journal - October 30, 2015 Category: Respiratory Medicine Authors: Kheirallah, A. K., Sayers, I., Hall, I. Tags: 3.1 Molecular Pathology and Functional Genomics Source Type: research

Late-breaking abstract: Inhibition of RC kinase is a novel therapeutic approach for the treatment of COPD and IPF
RC kinase is a novel serine/threonine kinase, expressed predominantly by pulmonary macrophage and type II bronchial epithelial cells. Examination of BAL macrophage mRNA isolated from COPD and IPF patients showed increased expression of RC kinase compared to normal smokers and non-smoking patients. In vitro studies showed an upregulation of RC kinase upon cell stress, including oxidative stress. This correlated with an increase of NF-kb activity and IL-8 production that could be inhibited by RC kinase siRNA or small molecule antagonists. Biochemical analysis revealed that RC kinase is predominantly a nuclear protein and int...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Boehme, S., Coelho, A., Hogaboam, C., Ly, T. W., Bacon, K., Athanacio, J. Tags: 5.1 Airway Pharmacology and Treatment Source Type: research

CREB/CRTC-mediated regulation of transcription is important for regulatory T cells
Conclusion: Our data point to an activation of CREB/CRTC-mediated transcription in naturally occurring as well as in in vitro induced Tregs. CREB knockdown reduced the formation of iTregs suggesting a possible role of this pathway in immune tolerance.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Bartel, S., Kastle, M., Eickelberg, O., Krauss-Etschmann, S. Tags: 5.3 Allergy and Immunology Source Type: research

Expression and function of aquaporin 1 in hypoxia-induced pulmonary hypertension
Conclusion: Hx modulates the expression of Aqp1 in vivo and in vitro. Inhibition of Aqp1 through siRNA resulted in less migration and more apoptosis. These data suggest an important functional role of Aqp1 in the development of hypoxia-induced PH.
Source: European Respiratory Journal - October 30, 2015 Category: Respiratory Medicine Authors: Schuoler, C., Haider, T., Leuenberger, C., Gassmann, M., Kohler, M., Huber, L., Brock, M. Tags: 4.3 Pulmonary Circulation and Pulmonary Vascular Disease Source Type: research

Reactive sulfur species are involved in cigarette smoke-induced cellular senescence
Conclusions: The current study suggests that the reduction in reactive sulfer species might be related to CS-induced cellular senescence.
Source: European Respiratory Journal - November 20, 2019 Category: Respiratory Medicine Authors: Yamanaka, S., Ichikawa, T., Sugiura, H., Numakura, T., Sano, H., Yamada, M., Fujino, N., Tanaka, R., Kyogoku, Y., Akaike, T., Ichinose, M. Tags: Molecular pathology and funct. genomics Source Type: research

IL-11 increases levels and activates circulating fibrocytes in different pulmonary hypertension animal models.
In conclusion, IL-11 promotes an increase of circulating fibrocytes, their adhesion to HPAECs and phenotypic switching to myofibroblast.
Source: European Respiratory Journal - December 1, 2022 Category: Respiratory Medicine Authors: Roger, I., Milara, J., Montero, P., Belhadj, N., Cortijo, J. Tags: 13.01 - Pulmonary hypertension Source Type: research

Novel strategies for genetic manipulation of human iPSC-derived organoid platforms
Conclusions: Our preliminary data demonstrates modest but successful transfection of patient iPSC-derived organoid cultures ‘in situ’ in 3D matrigel using a commercial transfection reagent. Further development of these methods will facilitate miRNA:Target gene interaction studies to complement ongoing research in iPSC organoid platforms and inform delivery of future therapeutic strategies utilising small RNA.
Source: European Respiratory Journal - December 1, 2022 Category: Respiratory Medicine Authors: Oglesby, I., De Santi, C., Schweikert, A., Cryan, S. A., Hurley, K. Tags: 03.02 - Airway cell biology and immunopathology Source Type: research

LSC 2014 abstract - Influenza infection of human lung macrophages increases PDL1 expression via autologous IFN{beta}
Lung macrophages are an important defence against influenza infection, but macrophage function can be dysregulated by infection. Recent work has shown that acute immune responses to influenza in the murine lung are regulated by PDL1 expression leading to rapid modulation of CD8+ T cell responses via the PD1 receptor1. This PD1/PDL1 pathway may modulate acute inflammatory responses to prevent tissue damage. The aim of the present study was to investigate how human macrophages regulate their PDL1 expression in response to influenza infection. Human lung and monocyte-derived macrophages (MDMs) were exposed to H3N2 X31 influen...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Staples, K., Spalluto, C. M., McKendry, R. T., Wilkinson, T. M. A. Tags: 10.1 Respiratory Infections Source Type: research

Late-breaking abstract: The effects and mechanism of adiponectin on inhibiting pulmonary fibrosis
Conclusions Overall, these studies indicated some protective effects of APN on PQ induced pulmonary fibrosis in a dose-dependent manner. There are APN and functional AdipoR1 expressed by human WI-38 lung fibroblasts, suggesting a potential application prospect of APN for lung fibrosis.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Yao, R., Cao, Y., He, Y.-r., Zeng, Z., Liang, Z.-a. Tags: 1.5 Diffuse Parenchymal Lung Disease Source Type: research

Loss of PTEN induced lung fibroblasts exhibiting similar pathogenic features to cancer cells in idiopathic pulmonary fibrosis
Conclusion: These findings indicate that lung fibroblasts have decreased PTEN expression in IPF. Inhibition of PTEN induced fibroblast activation and exhibiting similar pathogenic features to cancer cells.
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Geng, J., Huang, X., Dai, H. Tags: 1.5 Diffuse Parenchymal Lung Disease Source Type: research

Reduction of high mobility group nucleosome binding domain-5 protein promotes the development of emphysema
Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is associated with an enhanced chronic inflammation and development of emphysema. However, the mechanism by which genetic alteration contributes to empyhsema development is still barely understood. In a previous study we have detected spontaneous emphysema development in HMGN5 knockout mice (Kluger E.J., et. al., JBC 2013). The HMGN5 gene encodes a nucleosomal binding protein that competes with H1 on the nucleosome and loosens the structure of chromatin. It plays an important role in transcription, replication and the repair mechanism...
Source: European Respiratory Journal - December 23, 2014 Category: Respiratory Medicine Authors: Merthan, L., Bustin, M., Eickelberg, O., Yildirim, A. O. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research