Clostridium difficile Toxin A Induces Intestinal Epithelial Cell Apoptosis and Damage: Role of Gln and Ala-Gln in Toxin A Effects

被引：0
作者：
Gerly A. C. Brito
Benedito Carneiro-filho
Reinaldo B. Oriá
Raul V. Destura
Aldo A. M. Lima
Richard L. Guerrant
机构：
[1] University of Virginia,Center for Global Health, Department of Internal Medicine, School of Medicine
[2] Federal University of Ceará,Departments of Morphology, School of Medicine
[3] Federal University of Ceará,Department of UPC & IBIMED, School of Medicine
[4] University of Fortaleza,Department of Morphology, Health Science Center
[5] University of Virginia,Center for Global Health, Department of Internal Medicine, School of Medicine
来源：
Digestive Diseases and Sciences | 2005年 / 50卷
关键词：
toxin A; glutamine; alanyl-glutamine; apoptosis; migration; transepithelial resistance;
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摘要：
The aim of this study was to investigate the effect of Clostridium difficile toxin A (TxA) on intestinal epithelial cell migration, apoptosis, and transepithelial resistance and to evaluate the effect of glutamine (Gln) and its stable derivative, alanyl-glutamine (Ala-Gln), on TxA-induced damage. Migration was measured in rat intestinal epithelial cells (IEC-6) 6 and 24 hr after a razor scrape of the cell monolayer. Cell proliferation was indirectly measured utilizing the tetrazolium salt WST-1. The cells were incubated with TxA (1–100 ng/ml) in medium without Gln or medium containing Gln or Ala-Gln (1–30 mM). Apoptosis was quantified in IEC-6 cells using annexin V assay. Transepithelial resistance was measured using an epithelial voltohmmeter across T84 cells seeded on a transwell filter. TxA-induced a dose-dependent reduction of migration and also caused dose and time-dependent apoptosis in IEC-6 cells. Gln and Aln-Gln significantly enhanced IEC-6 cell migration and proliferation. Gln and Ala-Gln also prevented the inhibition of migration, apoptosis, and the initial drop in transepithelial resistance induced by TxA. In conclusion, both peptides reduced toxin-induced epithelial damage and thus might play an adjunctive role in C. difficile-induced colitis therapy.
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页码：1271 / 1278
页数：7
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