Activation of PPARgamma is not involved in butyrate-induced epithelial cell differentiation.

Histone deacetylase-inhibitors affect growth and differentiation of intestinal epithelial cells by inducing expression of several transcription factors, e.g. Peroxisome proliferator-activated receptor gamma (PPARgamma) or vitamin D receptor (VDR). While activation of VDR by butyrate mainly seems to be responsible for cellular differentiation, the activation of PPARgamma in intestinal cells remains to be elucidated. The aim of this study was to determine the role of PPARgamma in butyrate-induced cell growth inhibition and differentiation induction in Caco-2 cells. Treatment with PPARgamma ligands ciglitazone and BADGE (bisphenol A diglycidyl) enhanced butyrate-induced cell growth inhibition in a dose- and time-dependent manner, whereas cell differentiation was unaffected after treatment with PPARgamma ligands rosiglitazone and MCC-555. Experiments were further performed in dominant-negative PPARgamma mutant cells leading to an increase in cell growth whereas butyrate-induced cell differentiation was again unaffected. The present study clearly demonstrated that PPARgamma is involved in butyrate-induced inhibition of cell growth, but seems not to play an essential role in butyrate-induced cell differentiation.