Ms. Jacewicz et al., MATURATIONAL REGULATION OF GLOBOTRIAOSYLCERAMIDE, THE SHIGA-LIKE TOXIN-1 RECEPTOR, IN CULTURED HUMAN GUT EPITHELIAL-CELLS, The Journal of clinical investigation, 96(3), 1995, pp. 1328-1335
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.