Maturational regulation of globotriaosylceramide, the Shiga-like toxin 1 receptor, in cultured human gut epithelial cells

• Published in: The Journal of clinical investigation Vol. 96; no. 3; pp. 1328 - 1335
• Main Authors: Jacewicz, M S, Acheson, D W, Mobassaleh, M, Donohue-Rolfe, A, Balasubramanian, K A, Keusch, G T
• Format: Journal Article
• Language: English
• Published: United States 01.09.1995
• Subjects: Adenocarcinoma; Bacterial Toxins - isolation & purification; Bacterial Toxins - metabolism; Bacterial Toxins - toxicity; Butyrates - pharmacology; Butyric Acid; Cell Line; Cell Survival - drug effects; Colonic Neoplasms; Cycloheximide - pharmacology; Dactinomycin - pharmacology; Enterotoxins - metabolism; Epithelium - metabolism; Flow Cytometry; Gene Expression Regulation, Neoplastic - drug effects; Glycolipids - biosynthesis; Humans; Kinetics; Receptors, Cell Surface - biosynthesis; Shiga Toxin 1; Time Factors; Transcription, Genetic - drug effects; Trihexosylceramides - biosynthesis; Tumor Cells, Cultured
• ISSN: 0021-9738
• DOI: 10.1172/jci118168

Differentiated villus intestinal epithelial cells express globotriaosylceramide, the Shiga-like toxin 1 (SLT-1) receptor, and are sensitive to toxin-mediated cytotoxicity, whereas undifferentiated crypt cells neither express Gb3 nor respond to toxin. To investigate if SLT-1 receptors are maturationally regulated in human intestinal cells, we examined the effect of butyrate, a known transcriptional regulator of differentiation genes in many cell types, using cultured colonic cancer-derived epithelial cell lines. Exposure to butyrate increased villus cell marker enzymes such as alkaline phosphatase, sucrase, and lactase, expression of toxin receptors, and sensitivity to SLT-1 in villus-like CaCo-2A and HT-29 cells. These effects were reversibly inhibited by preincubation of CaCo-2A cells with actinomycin D or cycloheximide. Butyrate-treated CaCo-2A cells unable to bind fluoresceinated SLT-1 B subunit were undifferentiated as assessed by alkaline phosphatase activity. HT-29 cells induced to differentiate by another signal, glucose deprivation, upregulated receptor content and response to toxin. Crypt-like T-84 cells responded to butyrate with a modest increase in alkaline phosphatase and toxin binding, but no induction of sucrase or lactase, and no change in sensitivity to toxin. The results demonstrate that expression of SLT-1 toxin receptors and toxin sensitivity are coregulated with cellular differentiation in cultured intestinal cells.