Tight Junctions and CellCell Interactions

Chronic inflammation in mucosal tissues can influence epithelial barrier function via proinflammatory cytokines such as interferon (IFN)-γ and tumor necrosis factor-α. Increased mucosal levels of these cytokines have been observed in mucosal biopsies from patients with a chronic inflammatory condition referred to as inflammatory bowel disease. Paracellular permeability across epithelial cells is regulated by tight junctions (TJ_s ), which are the apical most junctions in epithelial cells. Given that pro-inflammatory cytokines modulate the epithelial barrier and that TJs regulate epithelial permeability, we analyzed the influence of IFN-γ on TJ function/structure. Our results suggest that IFN-γ induced a time-dependent increase in paracellular permeability that was associated with internalization of TJ transmembrane proteins, occludin, junction adhesion molecule A, and claudin-1. In this chapter, we focus on selected methods used to investigate the influence of IFN-? on epithelial barrier function.