Taurodeoxycholate Stimulates Intestinal Cell Proliferation and Protects Against Apoptotic Cell Death Through Activation of NF-κB

We hypothesized that the NF-κB pathway would be operative in the proliferative effect of bile salts on enterocytes. To determine this, we studied the effect of the bile salt taurodeoxycholate on cultured rat enterocyte proliferation and apoptosis and examined the role of NF-κB activation in these growth regulatory processes. Intestinal epithelial cells were grown for 6 days with or without taurodeoxycholate. Proliferation was measured. The cells were exposed to a known apoptotic stimulus, TNF-α and cyclohexamide. Apoptosis was quantified using cell number and the TUNEL stain. NF-κB activation was determined by an electrophoretic mobility shift assay. NF-κB activation was inhibited by an IκB superrepressor. Taurodeoxycholate stimulated cell proliferation (P<0.01) and induced resistance to TNF-α induced apoptosis (P<0.01). Taurodeoxycholate induced NF-κB activation. Inhibition of NF-κB prevented taurodeoxycholate-induced IEC-6 cell proliferation and rendered cells sensitive to TNF-α-induced apoptosis. Taurodeoxycholate stimulates intestinal epithelial cell proliferation and protects intestinal epithelial cells from TNF-α-induced apoptosis through NF-κB. These data support an important beneficial role of bile salts in regulation of mucosal growth and repair. Decreased enterocyte exposure to luminal bile salts, as occurs during starvation and parenteral nutrition, may have a detrimental effect on mucosal integrity.