Document Detail

Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins.
MedLine Citation:
PMID:  21617116     Owner:  NLM     Status:  Publisher    
Experimental models for esophageal epithelium in vitro either suffer from poor differentiation or complicated culture systems. An air-liquid interface (ALI) system with normal human bronchial epithelial (NHBE) cells can serve as a model of esophageal-like squamous epithelial cell layers. Here, we explore the influence of bile acids on barrier function and tight junction (TJ) proteins. The cells were treated with taurocholic acid (TCA), glycocholic acid (GCA), or deoxycholic acid (DCA) at different pH values, or with pepsin. Barrier function was measured by trans-epithelial electrical resistance (TEER) and the diffusion of paracellular tracers (permeability). The expression of TJ proteins, including claudin-1 and claudin-4, was examined by western blotting of 1% NP-40 soluble and insoluble fractions. TCA and GCA dose-dependently decreased TEER and increased paracellular permeability at pH 3 after 1 h. TCA (4 mM) or GCA (4 mM) did not change TEER and permeability at pH 7.4 or pH 4. The combination of TCA and GCA at pH 3 significantly decreased TEER and increased permeability at lower concentrations (2 mM). Pepsin (4 mg/ml, pH 3) did not have any effect on barrier function. DCA significantly decreased the TEER and increased permeability at pH 6, a weakly acidic condition. TCA (4 mM) and GCA (4 mM) significantly decreased the insoluble fractions of claudin-1 and claudin-4 at pH 3. In conclusion, acidic bile salts disrupted the squamous epithelial barrier function partly by modulating the amounts of claudin-1 and claudin-4. These results provide new insights for understanding the role of TJ proteins in esophagitis.
Xin Chen; Tadayuki Oshima; Toshihiko Tomita; Hirokazu Fukui; Jiro Watari; Takayuki Matsumoto; Hiroto Miwa
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-26
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  -     ISSN:  1522-1547     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1Hyogo College of Medicine.
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