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Cellular Tight Junctions as Mediators of Adverse Effects

Molecular and Cellular Aspects of Toxicology

  1. Yula Sambuy PhD

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat159

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Sambuy, Y. 2009. Cellular Tight Junctions as Mediators of Adverse Effects. General, Applied and Systems Toxicology. .

Author Information

  1. INRAN—National Research Institute for Food and Nutrition, Italy

Publication History

  1. Published Online: 15 DEC 2009

Abstract

Tight junctions are highly complicated and finely regulated structures that provide for the barrier and exchange functions of epithelia and endothelia at the interface between the internal organs and the external environment, and are therefore frequently exposed to noxious stimuli. Recent evidence points to epithelial and endothelial barrier dysfunction, resulting from changes in structure of the tight junctions, as an important early toxic event, preceding more severe damage to the cells. Increased tight junction permeability has also been implicated in the pathogenesis of several multifactorial diseases, frequently involving an exaggerated inflammatory response. Some examples of tight junction alterations occurring after exposure to toxic stimuli, including ethanol, heavy metals and oxidative stress, will be discussed in more detail. In addition, the implications of barrier dysfunction in pathological conditions including hereditary disorders of tight junction proteins, cancers, microbial infections, inflammatory bowel disease, multiple sclerosis and coeliac disease will be presented.

Keywords:

  • claudins;
  • occludin;
  • ethanol;
  • metals;
  • inflammation;
  • epithelium;
  • endothelium;
  • toxicity;
  • permeability;
  • microbial pathogens