Development of microbial-human enterocyte interaction: cholera toxin.
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 Gsalpha) 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.
Combined Program in Pediatric Gastroenterology and Nutrition, Harvard Medical School, Director, Developmental Gastroenterology Laboratory, Massachusetts General Hospital, 114 16th Street (114-3503), Charlestown, MA 02129-4404, U.S.A.
Lei
L
Lu
Manuel E
ME
Baldeon
Tor
T
Savidge
Charalabos
C
Pothoulakis
W Allan
WA
Walker
D000367:Age Factors; D000818:Animals; D002478:Cells, Cultured; D002771:Cholera / Q000503:physiopathology*; D002772:Cholera Toxin / Q000633:toxicity*; D000242:Cyclic AMP / Q000378:metabolism; D020895:Enterocytes / Q000382:microbiology*; D005260:Female; D016332:Fetal Tissue Transplantation; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000382:microbiology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014183:Transplantation, Heterologous; D015854:Up-Regulation
D002772:Cholera Toxin; D000242:Cyclic AMP