MATURATIONAL REGULATION OF GLOBOTRIAOSYLCERAMIDE, THE SHIGA-LIKE TOXIN-1 RECEPTOR, IN CULTURED HUMAN GUT EPITHELIAL-CELLS

Differentiated villus intestinal epithelial cells express globotriaosy lceramide, the Shiga-like toxin 1 (SLT-1) receptor, and are sensitive to toxin-mediated cytotoxicity, whereas undifferentiated crypt cells n either express Gb3 nor respond to toxin, To investigate if SLT-1 recep tors are maturationally regulated in human intestinal cells, we examin ed the effect of butyrate, a known transcriptional regulator of differ entiation genes in many cell types, using cultured colonic cancer-deri ved epithelial cell lines. Exposure to butyrate increased villus cell marker enzymes such as alkaline phosphatase, sucrase, and lactase, exp ression of toxin receptors, and sensitivity to SLT-1 in villus-like Ca Co-2A and HT-29 cells, These effects were reversibly inhibited by prei ncubation of CaCo-2A cells with actinomycin D or cycloheximide. Butyra te-treated CaCo-2A cells unable to bind fluoresceinated SLT-1 B subuni t were undifferentiated as assessed by alkaline phosphatase activity. HT-29 cells induced to differentiate by another signal, glucose depriv ation, upregulated receptor content and response to toxin. Crypt-like T-84 cells responded to butyrate with a modest increase in alkaline ph osphatase and toxin binding, but no induction of sucrase or lactase, a nd no change in sensitivity to toxin, The results demonstrate that exp ression of SLT-1 toxin receptors and toxin sensitivity are coregulated with cellular differentiation in cultured intestinal cells.