Butyrate may have a role in preventing ulcerative colitis, but its precise mechanism is unknown. Also, PPARgamma (peroxisome proliferator-activated receptor) is expressed at high levels both in the colonic epithelium and colon cancer cell lines, but no report was shown on the relationship between PPARgamma activation and the effect of butyrate. We investigated the effects of butyrate and PPARgamma agonist on paracellular permeability. To discover whether PPARgamma expressed in the cell lines treated with butyrate was functional or not, we transfected HT-29 cells with an acyl-CoA oxidase promoter-luciferase reporter plasmid containing a PPRE (peroxisome proliferator responsive element) and analyzed the luciferase activity. Butyrate and PPARgamma agonist significantly reduced paracellular permeability of the colon cell line (p < 0.05) and this effect indicated that butyrate and PPARgamma agonist decreased HT-29 cell growth and increased differentiation (p < 0.01). PPRE activation treated with butyrate was approximately four and a half times that in untreated cells (p < 0.01). These findings suggest that the effect of butyrate on paracellular permeability has apparently taken place through PPARgamma activation and this effect attributes to preventing inflammation of the colon. (C) 2002 Elsevier Science (USA). All rights reserved.