Clostridium difficile toxin A induces intestinal epithelial cell apoptosis and damage: Role of Gln and Ala-Gln in toxin A effects

Gerly A C Brito, Benedito Carneiro-Filho, Reinaldo B. Oriá, Raul V. Destura, Aldo A M Lima, Richard L. Guerrant*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1271-1278
Number of pages8
JournalDigestive diseases and sciences
Volume50
Issue number7
DOIs
StatePublished - Jul 2005

Keywords

  • Alanyl-glutamine
  • Apoptosis
  • Clostridium difficile toxin A
  • Glutamine
  • Migration
  • Transepithelial resistance

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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