Molecular physiology and pathophysiology of tight junctions IV. Regulationof tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells

The epithelial lining of the gastrointestinal tract forms a regulated, sele ctively permeable barrier between luminal contents and the underlying tissu e compartments. Permeability across the epithelium is, in part, determined by the rate-limiting barrier of the paracellular pathway-the most apical in tercellular junction referred to as the tight junction (TJ). The TJ is comp osed of a multiprotein complex that affiliates with the underlying apical a ctomyosin ring. TJ structure and function, and therefore epithelial permeab ility, are influenced by diverse physiological and pathological stimuli; he re we review examples of such stimuli that are detected at the cell surface . For example, luminal glucose induces an increase in paracellular permeabi lity to small molecules. Similarly, but by other means, cytokines and leuko cytes in the vicinity of the epithelium also regulate TJ structure and para cellular permeability by influencing the TJ protein complex and/or its asso ciation with the underlying actin cytoskeleton.