The tight junction in inflammatory disease: communication breakdown

Curr Opin Pharmacol. 2009 Dec;9(6):715-20. doi: 10.1016/j.coph.2009.06.022. Epub 2009 Jul 24.


The intestinal epithelium restricts free passage of toxic and infectious molecules from the gut lumen while allowing selective paracellular absorption across the tight junction. Inflammatory bowel disease (IBD) patients demonstrate a loss of tight junction barrier function, increased pro-inflammatory cytokine production, and immune dysregulation; however, the relationship between these events is incompletely understood. Although tight junction barrier defects are insufficient to cause experimental IBD, mucosal immune activation is altered in response to increased epithelial permeability. Thus, an evolving model suggests that barrier dysfunction may predispose or enhance disease progression and therapies targeted to specifically restore the barrier function may provide an alternative or supplement to immunology-based therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology*
  • Colitis / chemically induced
  • Colitis / metabolism
  • Disease Models, Animal
  • Drug Delivery Systems
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / physiopathology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / physiology
  • Models, Immunological
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism*
  • Tight Junctions / physiology