BACKGROUND AND OBJECTIVES:
Corticosteroids are anti-inflammatory drugs commonly used to treat inflammatory bowel disease, but do not benefit many patients of steroid (glucocorticoid resistance) or the needs of inappropriately high doses remission (glucocorticoid-dependent) to hold. Because of the role of intestinal epithelial cells in inflammatory bowel disease, we looked for the signaling of the glucocorticoid receptor and the effect of interleukin-1 beta as one of the most important pro-inflammatory cytokines in the intestinal cell epithelial IEC-6 and Caco-2.
methods:
effect of dexamethasone on activation of transcription containing glucocorticoid response elements was reporter assay using a measured construction. The effect was transrepression of nuclear factor (NF) kappaB inducible reporter construct monitored. was also used in IEC-6 cells immunocytochemistry glucocorticoid receptor translocation to be monitored.
RESULTS:
reporter gene mediated by the receptor and translocation of the receiver, the effects of dexamethasone on interleukin-1 beta significantly inhibited induced by dexamethasone. Dexamethasone inhibited interleukin-1 beta induces the transcription of NF-kappaB gene driven only in IEC-6 and not in Caco-2 cells. However, in Caco-2 cells overexpressing the glucocorticoid receptor resulted in a significant decrease in the activity of NF-kappa B, even in the absence of dexamethasone.
CONCLUSION:
These studies demonstrate that gene regulation of glucocorticoid receptors leads in the epithelial cells of the intestine contribute to the anti-inflammatory action of glucocorticoids in inflammatory bowel disease. The data are consistent with the notion that interleukin-1 beta in the resistance induced by the inflammatory reaction produced of steroids, which, in the treatment of patients with inflammatory bowel disease is a clinical problem current.
