Molecular mechanisms of deguelin-induced apoptosis in transformed human bronchial epithelial cells

2004 ◽  
Vol 68 (6) ◽  
pp. 1119-1124 ◽  
Author(s):  
Ho-Young Lee
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Induced Apoptosis

scholarly journals Ionizing radiation induces epithelial–mesenchymal transition in human bronchial epithelial cells

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Bo Tang ◽  
Yue Xi ◽  
Fengmei Cui ◽  
Jin Gao ◽  
Huiqin Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ionizing Radiation ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Migration Ability ◽  
Bronchial Epithelial ◽  
Mesenchymal Transition ◽  
Potential Biomarker

Abstract Objective: The present study aimed to analyze the mechanism by which long-term occupational exposure of workers to low-dose ionizing irradiation induces epithelial–mesenchymal transition (EMT) of the human bronchial epithelial cells using transcriptome profiling. Methods: RNA-seq transcriptomics was used to determine gene expression in blood samples from radiation-exposed workers followed by bioinformatics analysis. Normal bronchial epithelial cells (16HBE) were irradiated for different durations and subjected to immunofluorescence, Western blotting, scratch healing, and adhesion assays to detect the progression of EMT and its underlying molecular mechanisms. Results: Transcriptomics revealed that exposure to ionizing radiation led to changes in the expression of genes related to EMT, immune response, and migration. At increased cumulative doses, ionizing radiation-induced significant EMT, as evidenced by a gradual decrease in the expression of E-cadherin, increased vimentin, elevated migration ability, and decreased adhesion capability of 16HBE cells. The expression of fibronectin 1 (FN1) showed a gradual increase with the progression of EMT, and may be involved in EMT. Conclusion: Ionizing radiation induces EMT. FN1 may be involved in the progression of EMT and could serve as a potential biomarker for this process.

scholarly journals Corticosteroids, eosinophils and bronchial epithelial cells: new insights into the resolution of inflammation in asthma

2003 ◽  
Vol 178 (1) ◽  
pp. 37-43 ◽  
Author(s):  
GM Walsh ◽  
DW Sexton ◽  
MG Blaylock
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Bronchial Epithelial Cells ◽  
Membrane Receptors ◽  
Bronchial Epithelial ◽  
Anti Inflammatory ◽  
Macrophage Colony ◽  
High Doses ◽  
Induced Apoptosis ◽  
Receptor Ligation

Anti-inflammatory therapy in asthma is reliant on corticosteroids, particularly in their inhaled form. However, steroids are rather non-specific in their actions and they also raise concerns regarding compliance and side-effect Issues. Furthermore, a small proportion of patients with asthma fail to respond to oral glucocorticoids even at high doses. This Article will review the role that steroids and membrane receptor ligation play in the induction of eosinophil apoptosis together with the mechanisms by which corticosteroids enhance the disposal of apoptotic eosinophils by both professional and non-professional phagocytes. Eosinophils are thought to be the major pro-inflammatory effector cell in asthma and their persistence in the airways is probably enhanced by the presence of several asthma-relevant cytokines that prolong eosinophil survival by inhibition of apoptosis (interleukin (IL)-3, IL-5, granulocyte-macrophage colony-stimulating factor, IL-9, IL-13, IL-15). In contrast, a number of signals have been described that accelerate apoptosis in human eosinophils including corticosteroids or ligation of membrane receptors (CD95, CD45, CD69). Thus, the load of lung eosinophils in asthmatic disease is likely to be related to a balance in the tIssue microenvironment between pro- and anti-apoptotic signals. Furthermore, removal of apoptotic eosinophils by phagocytosis by alveolar macrophages or bronchial epithelial cells in a specific receptor-mediated way is as important as the process of apoptosis induction. Corticosteroids enhance the recognition and engulfment of apoptotic eosinophils by macrophages or bronchial epithelial cells. Caspases are key intracellular molecules in the control of apoptosis and defects in caspase-induced apoptosis in eosinophils from steroid-resistant individuals may contribute to the molecular mechanisms underlying glucocorticoid insensitivity in these cells. These findings point the way to new and more targeted anti-inflammatory therapy for asthma and may provide important clues for the development of alternative therapies for glucocorticoid resistance.

scholarly journals Thiazolidinediones induce proliferation of human bronchial epithelial cells through the GPR40 receptor

2009 ◽  
Vol 296 (6) ◽  
pp. L970-L978 ◽  
Author(s):  
Delphine Gras ◽  
Pascal Chanez ◽  
Valérie Urbach ◽  
Isabelle Vachier ◽  
Philippe Godard ◽  
...  
Keyword(s):  
Cell Growth ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Receptor Activation ◽  
Airway Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Peroxisome Proliferator ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Intracellular Ca

Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor-γ (PPARγ) ligands that are widely used in type II diabetes treatment. In addition to their ability to improve glucose homeostasis, TZDs possess anti-inflammatory properties and inhibit growth of many cells, particularly cancerous airway epithelial cells. However, the functional effects of PPARγ ligands on nonmalignant human bronchial epithelial cells have never been investigated. In the present study, we questioned whether PPARγ ligands may regulate proliferation of human bronchial epithelial cells, and we studied their potential molecular mechanisms. We found that synthetic PPARγ agonists, rosiglitazone (RGZ) and troglitazone (TGZ), induced proliferation of human bronchial epithelial cells, whereas the endogenous PPARγ ligand, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), inhibited cell growth. RGZ and TGZ (10 μM) induced a rapid and transient intracellular Ca2+ mobilization from thapsigargin-sensitive intracellular stores, whereas 15d-PGJ2 (5 μM) did not induce any Ca2+ signal. The PPARγ antagonist GW-9662 did not inhibit any biological responses, but it reversed the effect of 15d-PGJ2 on cell growth. Using RT-PCR, we detected mRNA expression of the GPR40 receptor, a G protein-coupled receptor recently identified as a receptor for free fatty acids and TZDs, in human bronchial epithelial cells. Downregulation of GPR40 by small-interfering RNA led to a significant inhibition of TZD-induced Ca2+ mobilization and proliferation. This study provides evidence for the proliferative effect of anti-diabetic drug TZDs in nonmalignant human bronchial epithelial cells through GPR40 receptor activation, involving an intracellular Ca2+ signaling pathway.

scholarly journals Molecular Mechanisms of Anti-Inflammatory Action of Erythromycin in Human Bronchial Epithelial Cells: Possible Role in the Signaling Pathway That Regulates Nuclear Factor-κB Activation

2004 ◽  
Vol 48 (5) ◽  
pp. 1581-1585 ◽  
Author(s):  
Masashi Desaki ◽  
Hitoshi Okazaki ◽  
Toshiaki Sunazuka ◽  
Satoshi Omura ◽  
Kazuhiko Yamamoto ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Nuclear Factor Κb ◽  
Bronchial Epithelial Cells ◽  
Nuclear Factor ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Anti Inflammatory ◽  
Inflammatory Action

ABSTRACT Long-term macrolide therapy has been proven to improve survival in patients with diffuse panbronchiolitis. Although its mechanisms remain unknown, previous studies have suggested the effects of macrolide might be anti-inflammatory rather than antibacterial. To elucidate the molecular mechanisms of its action, we studied here the effects of erythromycin (EM) and its new derivative, EM703, which shows no antibacterial action, on the activation of the transcription factor nuclear factor-κB (NF-κB) in human bronchial epithelial cells. Western blotting analysis showed that EM did not inhibit the degradation of IκBα, suggesting the molecular target for EM was not the dissociation of NF-κB from IκB. An electrophoretic mobility shift assay showed that EM did not interrupt the NF-κB DNA-binding activity in the nucleus under the conditions tested. Moreover, not only EM but also EM703 suppressed the activation of NF-κB and the production of interleukin-8, demonstrating that the anti-inflammatory action of the macrolide is independent of its antibacterial activity. Taken together, these data suggest EM has an anti-inflammatory action, presumably via an interaction with the NF-κB signaling pathway in the downstream of the dissociation from IκB, resulting in the inhibition of NF-κB.

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