Document Detail


Hypoxia down-regulates glucocorticoid receptor alpha and attenuates the anti-inflammatory actions of dexamethasone in human alveolar epithelial A549 cells.
MedLine Citation:
PMID:  19450611     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Glucocorticoids (GCs) are frequently used to treat various pulmonary diseases, which are typically accompanied by hypoxia. Whether hypoxia influences the effects of GCs on human airway cells remains unclear. The aim of the present study was to characterize changes in the expression levels of two isoforms of the glucocorticoid receptor (GR) and to evaluate the anti-inflammatory actions of GCs under hypoxic conditions in A549 cells. MAIN METHODS: A549 cells were exposed to normoxic or hypoxic conditions for 24, 48 and 72 h. Morphological alterations of cells were captured using a differential interference contrast microscope (DIC), and cell cycle distribution was estimated by flow cytometry. Real-time quantitative polymerase chain reaction and western blot were used to determine the mRNA and protein expression levels of GRalpha and GRbeta. Radioimmunoassay (RIA) for interleukin (IL)-8 was used to assess the anti-inflammatory actions of GCs after cells were stimulated with lipopolysaccharide (LPS). KEY FINDINGS: After cells were exposed to hypoxic conditions for 48 h, visible morphological alterations in the cells were observed. Cell cycle analysis showed that the number of cells in G1 phase increased significantly under hypoxia compared to the normoxic conditions. Hypoxia caused a time-dependent decrease in both mRNA and protein expression levels for GRalpha, but not GRbeta. Furthermore, when exposed to hypoxia for 48 h, the inhibitory effects of dexamethasone on LPS-stimulated IL-8 release were attenuated. SIGNIFICANCE: These results indicate that hypoxia impairs the anti-inflammatory actions of GCs in A549 cells, which could be attributed to down-regulation of GRalpha expression under hypoxic conditions.
Authors:
Yan Huang; Ji-Jing Zhao; Yuan-Yuan Lv; Pei-Shan Ding; Rong-Yu Liu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-18
Journal Detail:
Title:  Life sciences     Volume:  85     ISSN:  1879-0631     ISO Abbreviation:  Life Sci.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-26     Completed Date:  2009-07-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  107-12     Citation Subset:  IM    
Affiliation:
Department of Pulmonary Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei 230022, Anhui, China.
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MeSH Terms
Descriptor/Qualifier:
Anoxia / metabolism*,  pathology
Anti-Inflammatory Agents / pharmacology*
Cell Line
Cell Proliferation
Dexamethasone / pharmacology*
Down-Regulation
Humans
Interleukin-8 / antagonists & inhibitors,  metabolism
Protein Isoforms / biosynthesis
Pulmonary Alveoli / drug effects*,  metabolism,  pathology
Receptors, Glucocorticoid / biosynthesis*
Respiratory Mucosa / drug effects*,  metabolism,  pathology
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Interleukin-8; 0/Protein Isoforms; 0/Receptors, Glucocorticoid; 0/glucocorticoid receptor alpha; 0/glucocorticoid receptor beta; 50-02-2/Dexamethasone

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