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Article
Interleukin-1β Mediates β-Catenin-Driven Downregulation of Claudin-3 and Barrier Dysfunction in Caco2 Cells
Digestive Diseases and Sciences
(2016)
Abstract
Background 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.
Methods and Results 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.
Conclusions Taken together, these data represent the first line of evidence demonstrating nmMLCK regulation of claudin-3 expression in response to IL-1β-treated epithelial cells.
Keywords
- claudin-3,
- interleukin-1β,
- β catenin,
- non-muscle myosin light chain kinase,
- epithelial barrier,
- permeability
Disciplines
Publication Date
August, 2016
DOI
10.1007/s10620-016-4145-y
Citation Information
R. J. Haines, R. S. Beard, L. Chen, R. A. Eitnier, et al.. "Interleukin-1β Mediates β-Catenin-Driven Downregulation of Claudin-3 and Barrier Dysfunction in Caco2 Cells" Digestive Diseases and Sciences Vol. 61 Iss. 8 (2016) p. 2252 - 2261 ISSN: 01632116 Available at: http://works.bepress.com/richard-beard/2/