Physiol 279: G851–G857, 2000.—The epithelial lining of the gastrointestinal tract forms a regulated, selectively permeable barrier between luminal contents and the underlying tissue compartments. Permeability across the epithelium is, in part, determined by the rate-limiting barrier of the paracellular pathway—the most apical intercellular junction referred to as the tight junction (TJ). The TJ is composed of a multiprotein complex that affiliates with the underlying apical actomyosin ring. TJ structure and function, and therefore epithelial permeability, are influenced by diverse physiological and pathological stimuli; here we review examples of such stimuli that are detected at the cell surface. For example, luminal glucose induces an increase in paracellular permeability to small molecules. Similarly, but by other means, cytokines and leukocytes in the vicinity of the epithelium also regulate TJ structure and paracellular permeability by influencing the TJ protein complex and/or its association with the underlying actin cytoskeleton. epithelial cells; leukocytes

THE EPITHELIAL LINING of the gastrointestinal tract forms a regulated, selectively permeable barrier permitting the passive entry of luminal nutrients, ions, and water while restricting pathogen access to underlying tissue compartments. Permeability properties of the epithelium are dynamically regulated by diverse physiological and pathological stimuli (25). Additionally, enhanced paracellular permeability across intestinal epithelium occurs in patients with Crohn’s disease as well as their first-degree relatives, suggesting that altered tight junction (TJ) permeability may be a contributing factor in this process (18). Similarly, altered