Nitric oxide and intestinal barrier failure

E. P. Nadler, J. S. Upperman, E. C. Dickinson, H. R. Ford

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


The systemic inflammatory response syndrome (SIRS) is a leading cause of morbidity and mortality in adults and children. Various proinflammatory mediators have been implicated in the pathogenesis of SIRS; however, their mechanisms of action are poorly defined. Recent evidence suggests that nitric oxide (NO) plays a regulatory role in gut barrier function. Sustained upregulation of NO production in the intestine can lead to intestinal epithelial injury through the formation of peroxynitrite. Peroxynitrite can nitrate mitochondrial proteins and inhibit cellular respiration. The resultant changes in mitochondrial function lead to activation of the caspase cascade, subsequent DNA fragmentation, and enterocyte apoptosis. Enterocyte apoptosis results in a transient 'bare area' in the intestinal epithelium where bacteria can attach and then penetrate the lamina propria. Bacteria that successfully escape the immune system may in turn incite a systemic inflammatory response.

Original languageEnglish (US)
Pages (from-to)148-154
Number of pages7
JournalSeminars in Pediatric Surgery
Issue number3
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery


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