Interleukin-1ß Mediates ß-Catenin-Driven Downregulation of Claudin-3 and Barrier Dysfunction in Caco2 Cells.
Dig Dis Sci
; 61(8): 2252-2261, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27074920
ABSTRACT
BACKGROUND:
IL-1ß is a cytokine involved in mediating epithelial barrier dysfunction in the gut. It is known that IL-1ß mediates activation of non-muscle myosin light chain kinase in epithelial cells, but the precise mechanism by which epithelial barrier dysfunction is induced by IL-1ß is not understood. METHODS ANDRESULTS:
Using a Caco2 cell model, we show that the expression of the tight junction protein, claudin-3, is transcriptionally downregulated by IL-1ß treatment. In addition, after assessing protein and mRNA expression, and protein localization, we show that inhibition of nmMLCK rescues IL-1ß-mediated decrease in claudin-3 expression as well as junction protein redistribution. Using chromatin immunoprecipitation assays, we also show that ß-catenin targeting of the claudin-3 promoter occurs as a consequence of IL-1ß-mediated epithelial barrier dysfunction, and inhibition of nmMLCK interferes with this interaction.CONCLUSIONS:
Taken together, these data represent the first line of evidence demonstrating nmMLCK regulation of claudin-3 expression in response to IL-1ß-treated epithelial cells.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Permeabilidade
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RNA Mensageiro
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Junções Íntimas
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Beta Catenina
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Interleucina-1beta
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Claudina-3
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Mucosa Intestinal
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article