A porous defense: The leaky epithelial barrier in intestinal disease

Daniel R. Clayburgh, Le Shen, Jerrold R. Turner

Research output: Contribution to journalShort surveypeer-review

386 Scopus citations


A critical function of the intestinal mucosa is to form a barrier that separates luminal contents from the interstitium. This intestinal barrier is compromised in a number of intestinal diseases, most notably inflammatory bowel disease. In vitro studies have demonstrated that cytokines elaborated by immune cells can cause the mucosal barrier to become leaky; these cytokines are known to be increased in intestinal mucosa involved in inflammatory bowel disease. Detailed information describing the mechanisms by which altered cytokine signaling occurs is not available, but recent data implicate the cytoskeleton within epithelial cells as a critical regulator of the mucosal barrier under physiological and pathophysiological conditions. Using available data, we describe a model of intestinal disease where an initial insult to the epithelial barrier may trigger a self-amplifying cycle of immune activation, cytokine release, and further barrier dysfunction. This model is supported by the observation that pharmacological abrogation of cytokine signaling corrects both barrier defects and clinical disease in animal models and human patients, although such therapy clearly has multiple mechanisms. Other therapeutic targets that represent strategies to prevent or reverse disease processes are also considered. The overarching hypothesis is that modulation of the mucosal epithelial barrier plays a critical role in the initiation and propogation of inflammatory intestinal diseases.

Original languageEnglish (US)
Pages (from-to)282-291
Number of pages10
JournalLaboratory Investigation
Issue number3
StatePublished - 2004
Externally publishedYes


  • Cytokines
  • Cytoskeleton
  • Inflammatory bowel disease
  • Tight junction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'A porous defense: The leaky epithelial barrier in intestinal disease'. Together they form a unique fingerprint.

Cite this