The nuclear hormone receptor peroxisome proliferator-activated gamma (PPARgamma) is expressed as two isoforins (PPARgamma1 and gamma2), and is an important modulator of monocyte gene regulation and function. TGF-beta(1) is an essential and potent immune modulator and we therefore examined its effect on PPARgamma expression in human THP-1 monocytes. TGF-beta(1) strongly induced PPARgamma2 mRNA and protein expression with a lesser effect on PPARgamma1. Transcription from a PPARgamma2 promoter/luciferase reporter vector was activated approximately 3-fold by TGFbeta(1). Mutation of two C/EBP elements within the PPARgamma2 promoter reduced TGF-beta(1)-induced transcription by approximately 65'%. TGF-beta(1) also induced the expression of three C/EBPisoforms (alpha, beta, and delta). Induction of PPARgamma1 and gamma2 in monocytes by TGF-beta(1) may contribute to the anti-inflammatory effects of this growth factor. (C) 2002 Elsevier Science (USA). All rights reserved.