Document Detail

Exposure of airway epithelium to bile acids associated with gastroesophageal reflux symptoms: a relation to transforming growth factor-beta1 production and fibroblast proliferation.
MedLine Citation:
PMID:  17908704     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Gastroesophageal reflux (GER) is common in patients with various airway diseases. Airway epithelial cells can release growth factors that promote fibroblast proliferation. Exposure of airway epithelium to bile acids may induce a fibrotic response. OBJECTIVES: To determine how bile acids interact with airway epithelium; particularly, whether transforming growth factor-beta1 secretion and fibroblast proliferation are affected. METHODS: Induced sputum from patients with asthma, GER, or asthma associated with GER symptoms, or from healthy control subjects was collected. Total bile acids were measured by a spectrophotometric enzymatic assay. The major components of bile acids, chenodeoxycholic acid (CD) and glycochenodeoxycholic acid (GCD), were used to stimulate primary airway epithelial cells. Quantitative polymerase chain reaction and Western blotting were applied for messenger RNA expression and signal pathway analysis, respectively. Conditioned medium following CD stimulation was coincubated with fibroblasts for proliferation study. RESULTS: The amount of total bile acids in induced sputum was significantly higher in patients with GER and asthma-associated GER symptoms compared to that of healthy control subjects (p<0.005). CD, but not GCD, significantly induced TGF-beta1 production. TGF-beta1 messenger RNA expression was 2.5-fold increased compared to unstimulated cells. This occurred via p38 mitogen-activated protein (MAP) kinase and activating transcription factor-2 activation. Pretreatment with dexamethasone inhibited TGF-beta1 production at both messenger RNA and protein levels by inhibiting p38 MAP kinase phosphorylation. Conditioned medium from CD-treated epithelial cells enhanced fibroblast proliferation. CONCLUSIONS: Aspiration of bile acids may induce airway fibrosis through the production of TGF-beta1 and fibroblast proliferation. Early intervention to attenuate these processes may reduce fibrogenesis in various airway diseases associated with GER.
Diahn-Warng Perng; Kuo-Ting Chang; Kang-Cheng Su; Yu-Chung Wu; Mo-Tzu Wu; Wen-Hu Hsu; Chun-Ming Tsai; Yu-Chin Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-01
Journal Detail:
Title:  Chest     Volume:  132     ISSN:  0012-3692     ISO Abbreviation:  Chest     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-13     Completed Date:  2008-01-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1548-56     Citation Subset:  AIM; IM    
Department of Chest Medicine, Taipei Veterans General Hospital and School of Medicine, Nathional Yang-Ming University, 201, Section 2, Shih-Pai Rd, Taipei 11217, Taiwan.
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MeSH Terms
Analysis of Variance
Asthma / complications*,  pathology,  physiopathology
Bile Acids and Salts*
Blotting, Western
Case-Control Studies
Cell Proliferation
Culture Media, Conditioned
Epithelial Cells / cytology,  metabolism
Fibrosis / pathology,  physiopathology
Gastroesophageal Reflux / complications*,  pathology,  physiopathology
MAP Kinase Signaling System / physiology
Middle Aged
Respiratory Mucosa / cytology,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Statistics, Nonparametric
Transforming Growth Factor beta1 / metabolism*
p38 Mitogen-Activated Protein Kinases / metabolism
Reg. No./Substance:
0/Bile Acids and Salts; 0/Culture Media, Conditioned; 0/Transforming Growth Factor beta1; EC Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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