| Bile acids modulate tight junction structure and barrier function of Caco-2 monolayers via EGFR activation. | |
| | |
MedLine Citation:
|
PMID: 18239063 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Intestinal and systemic illnesses have been linked to increased gut permeability. Bile acids, whose luminal profile can be altered in human disease, modulate intestinal paracellular permeability. We investigated the mechanism by which selected bile acids increase gut permeability using a validated in vitro model. Human intestinal Caco-2 cells were grown in monolayers and challenged with a panel of bile acids. Transepithelial electrical resistance and luminal-to-basolateral fluxes of 10-kDa Cascade blue-conjugated dextran were used to monitor paracellular permeability. Immunoprecipitation and immunoblot analyses were employed to investigate the intracellular pathway. Redistribution of tight junction proteins was studied by confocal laser microscopy. Micromolar concentrations of cholic acid, deoxycholic acid (DCA), and chenodeoxycholic acid (CDCA) but not ursodeoxycholic acid decreased transepithelial electrical resistance and increased dextran flux in a reversible fashion. Coincubation of 50 muM CDCA or DCA with EGF, anti-EGF monoclonal antibody, or specific src inhibitor 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP-2) abolished the effect. A concentration of 50 muM of either CDCA or DCA also induced EGF receptor phosphorylation, occludin dephosphorylation, and occludin redistribution at the tight junction level in the same time frame and in a reversible fashion. We conclude that selected bile acids modulate intestinal permeability via EGF receptor autophosphorylation, occludin dephosphorylation, and rearrangement at the tight junction level. The effect is mediated by the src family kinases and is abolished by EGF treatment. These data also support the role of bile acids in the genesis of necrotizing enterocolitis and the protective effect of EGF treatment. |
| | |
Authors:
|
Francesco Raimondi; Pasquale Santoro; Maria Vittoria Barone; Serena Pappacoda; Maria Luisa Barretta; Merlin Nanayakkara; Carmela Apicella; Letizia Capasso; Roberto Paludetto |
Related Documents
:
|
17135343 - The hypolipidemic agent guggulsterone regulates the expression of human bile salt expor... 207803 - A convenient synthesis of 3-keto bile acids by selective oxidation of bile acids with s... 22385623 - Effect of salicylic acid on fusarium graminearum, the major causal agent of fusarium he... |
Publication Detail:
|
Type: Journal Article Date: 2008-01-31 |
Journal Detail:
|
Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 294 ISSN: 0193-1857 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2008 Apr |
Date Detail:
|
Created Date: 2008-04-09 Completed Date: 2008-05-22 Revised Date: 2009-11-19 |
Medline Journal Info:
|
Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: G906-13 Citation Subset: IM |
Affiliation:
|
Division of Neonatology, Department of Pediatrics, "Federico II" University, Naples, Italy. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antibodies, Monoclonal Bile Acids and Salts / metabolism* Caco-2 Cells Chenodeoxycholic Acid / metabolism Cholic Acid / metabolism Deoxycholic Acid / metabolism Dextrans / metabolism Electric Impedance Enzyme Activation Epidermal Growth Factor / metabolism Humans Intestinal Mucosa / drug effects, enzymology, metabolism* Kinetics Membrane Proteins / metabolism Organometallic Compounds / metabolism Organophosphorus Compounds / metabolism Permeability Phosphorylation Protein Kinase Inhibitors / pharmacology Pyrimidines / pharmacology Receptor, Epidermal Growth Factor / immunology, metabolism* Tight Junctions / drug effects, enzymology, metabolism* src-Family Kinases / antagonists & inhibitors, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/AG 1879; 0/Antibodies, Monoclonal; 0/Bile Acids and Salts; 0/Membrane Proteins; 0/Organometallic Compounds; 0/Organophosphorus Compounds; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 0/occludin; 1325-87-7/Cascade Blue; 474-25-9/Chenodeoxycholic Acid; 62229-50-9/Epidermal Growth Factor; 81-25-4/Cholic Acid; 83-44-3/Deoxycholic Acid; 9004-54-0/Dextrans; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.2/src-Family Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Metallothionein is a crucial protective factor against Helicobacter pylori-induced gastric erosive l...
Next Document: German science and black racism--roots of the Nazi Holocaust.