Regulation of nuclear factor-kappaB in intestinal epithelial cells in a cell model of inflammation.

BACKGROUND Interleukin-1 (IL-1), an inflammatory cytokine whose levels are elevated in inflamed mucosa, causes part of its effect on intestinal epithelial cells (IEC) through inducing ceramide production. AIM To study the role of nuclear factor-kappaB (NF-kappaB), a pro-inflammatory and anti-apoptotic factor, in IL-1-treated IEC. METHODS NF-kappaB activity and levels of apoptotic proteins were assessed by electrophoretic mobility shift assay and RNA-protection assay, respectively. RESULTS IL-1 and ceramide, which have been shown to partially mediate IL-1 effects on IEC, activated NF-kappaB levels significantly. This activation was due to a decrease in IkappaB-alpha and IkappaB-beta protein levels. Moreover, the ratio of mRNA levels of anti-apoptotic to pro-apoptotic proteins was significantly increased in IL-1-treated IEC. CONCLUSION NF-kappaB may play a key role in the regulation of the expression of pro-inflammatory and/or apoptotic genes in inflammatory bowel disease, making this protein an attractive target for therapeutic intervention.