ABSTRACT
OBJECTIVE AND DESIGN: Epigenetic regulation is important in the activation of inflammatory cells. In the present study, we evaluated if DNA-methylation variations are involved in Interleukin-1ß (IL-1ß)-induced intestinal epithelial cells activation. MATERIALS AND METHODS: Differentiated Caco-2 cells were exposed to IL-1ß or to 5-azadeoxycytidine (5-azadC) for 24 or 48 h. Genome-wide methylation status was evaluated, while DNA methylation status at the promoter region of the gene encoding interleukin-6, 8 and 10 (IL-6, 8 and 10) was estimated. The levels of the corresponding gene products as well as DNA methyltransferases (DNMTs) quantity were assessed. RESULTS: IL-1ß decreased genomic methylation of human intestinal epithelial cells and induced demethylation at cg-specific sites at the promoter of pro-inflammatory genes IL6 and IL8; conversely it did not change the methylation of the IL10 promoter. IL-1ß also increased the release of IL-6 and IL-8 but did not change the IL-10 expression. Finally, cell exposure to IL-1ß decreased the DNMT3b expression, increased DNMT3a and was not able to change DNMT1 expression. CONCLUSIONS: Our results suggest a potential role of IL-1ß as modulator of DNA methylation in activated differentiated Caco-2 cell line.
