Abstract
Diarrhea in infants and children is a major health hazard worldwide. Certain toxigenic diarrheas occur more commonly and are manifested more severely during the neonatal period. We have previously studied the regulation of cholera toxin–induced secretion in animal models during development. In those studies we have shown that cholera toxin stimulates a much greater secretion by immature compared with mature small intestine, and the mechanism appears to be an up-regulation of postreceptor signal transduction molecules (adenyl cyclase and Gsα) leading to an elevated cAMP level. In this study, using experimental models of human intestinal development (fetal cell lines, a micro-Ussing chamber, organ cultures, and fetal intestinal xenograft transplants), we provide preliminary evidence that cholera toxin induces an enhanced secretion mediated in part by a developmental up-regulation of the cAMP response in immature versus mature human small intestine. Additional studies are needed, however, to further define whether other developmental events (e.g. receptor expression) also regulate cholera toxin–enterocyte-enhanced interaction. Nonetheless, this approach to determining the role of development in the pathophysiology of cholera in infants may help in strategies to prevent and treat this condition and other age-related intestinal infectious diseases.
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Abbreviations
- CT:
-
cholera toxin
- I sc :
-
short circuit current
- T84:
-
a human colonic cancer cell line
- H4:
-
a primary human fetal crypt small intestinal cell line
- tsHFIE:
-
a temperature-sensitive, conditionally immortalized human fetal intestinal epithelial villous cell line
- PGE2:
-
prostaglandin E2
- SCID:
-
severe combined immunodeficiency
- CFTR:
-
cystic fibrosis transmembrane conductance regulator
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Supported by grants from the National Institutes of Health T32-DK07477 (L.L.); R37-HD12437; R01-HD31852; P01-DK33506; P30-DK40561 (W.A.W.)].
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Lu, L., Baldeon, M., Savidge, T. et al. Development of Microbial-Human Enterocyte Interaction: Cholera Toxin. Pediatr Res 54, 212–218 (2003). https://doi.org/10.1203/01.PDR.0000074974.21797.83
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DOI: https://doi.org/10.1203/01.PDR.0000074974.21797.83
