Inhibitory effect of peroxisome proliferator-activated receptor-γ ligands on the expression of IgE heavy chain germline transcripts in the human B cell line DND39

Abstract

The expression of ε germline transcripts (εGT) 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 εGT expression in the human B cell line DND39. We show here that the PPARγ ligand, 15-deoxy- Δ 12,14-prostaglandin J 2 (15d-PGJ 2), can suppress εGT expression at 1 μM without inhibiting cell proliferation. A synthetic and PPARγ-specific ligand, ciglitazone, also suppressed εGT expression in a dose-dependent manner at concentrations between 10 and 50 μM . Agonists for other PPAR isoforms did not affect εGT expression at concentrations between 0.01 and 10 μM . We also demonstrated that 1 μM 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 εGT expression. Therefore, the suppression of STAT6 phosphorylation by 15d-PGJ 2 is thought to participate in the inhibition of εGT expression. These results suggest that PPARγ ligands inhibit IL-4-induced IgE class switching in B lymphocytes.