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Crohn's disease (CD) patients have an abnormal increase in intestinal epithelial permeability. The defect in intestinal tight junction (TJ) barrier has been proposed as an important etiologic factor of CD. TNF-α increases intestinal TJ permeability. Because TNF-α levels are markedly increased in CD, TNF-α increase in intestinal TJ permeability could be a contributing factor of intestinal permeability defect in CD. Our purpose was to determine some of the intracellular mechanisms involved in TNF-α modulation of intestinal epithelial TJ permeability by using an in vitro intestinal epithelial system consisting of filter-grown Caco-2 monolayers. TNF-α produced a concentration- and time-dependent increase in Caco-2 TJ permeability. TNF-α-induced increase in Caco-2 TJ permeability correlated with Caco-2 NF-κB activation. Inhibition of TNF-α-induced NF-κB activation by selected NF-κB inhibitors, curcumin and triptolide …