Interleukin-1β Mediates β-Catenin-Driven Downregulation of Claudin-3 and Barrier Dysfunction in Caco2 Cells.

Interleukin-1β Mediates β-Catenin-Driven Downregulation of Claudin-3 and Barrier Dysfunction in Caco2 Cells.
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DOI:
10.1007/s10620-016-4145-y
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发表时间:
2016-08
影响因子:
3.1
通讯作者:
Wu MH
Wu MH
中科院分区:
医学3区
文献类型:
--
作者:
Haines RJ;Beard RS Jr;Chen L;Eitnier RA;Wu MH

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IL-1β is a cytokine involved in mediating epithelial barrier dysfunction in the gut. It is known that IL-1β 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-1β is not understood. Using a Caco2 cell model, we show that the expression of the tight junction protein, claudin-3, is transcriptionally downregulated by IL-1β treatment. In addition, after assessing protein and mRNA expression, and protein localization, we show that inhibition of nmMLCK rescues IL-1β mediated decrease in claudin-3 expression as well as junction protein redistribution. Using chromatin immunoprecipitation assays, we also show that β-catenin targeting of the claudin-3 promoter occurs as a consequence of IL-1β mediated epithelial barrier dysfunction, and inhibition of nmMLCK interferes with this interaction. Taken together, this data represent the first line of evidence demonstrating nmMLCK regulation of claudin-3 expression in response to IL-1β treated epithelial cells.
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