The expression of E: germline transcripts (epsilonGT) induced by interleukin (IL)-4 stimulation is essential for the progression of IgE-directed class switching. In this study, we examined the effects of various ligands for their ability to bind to the peroxisome proliferator-activated receptors (PPARs) and to modify the IL-4-induced epsilonGT expression in the human B cell line DND39. We show here that the PPARgamma ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), can suppress FGT expression at 1 muM without inhibiting cell proliferation. A synthetic and PPARgamma-specific ligand, ciglitazone, also suppressed FGT expression in a dose-dependent manner at concentrations between 10 and 50 muM. Agonists for other PPAR isoforms did not affect epsilonGT expression at concentrations between 0.01 and 10 muM. We also demonstrated that 1 muM 15d-PGJ(2) was able to suppress the IL-4-induced phosphorylation of the Signal Transducer and Activator of Transcription 6 (STAT6), which is a transcription factor essential for epsilonGT expression. Therefore, the suppression of STAT6 phosphorylation by 15d-PGJ(2) is thought to participate in the inhibition of epsilonGT expression. These results suggest that PPARgamma ligands inhibit IL-4-induced IgE class switching in B lymphocytes. (C) 2002 Elsevier Science (USA). All rights reserved.