Inhibitory effect of peroxisome proliferator-activated receptor-gamma ligands on the expression of IgE heavy chain germline transcripts in the human B cell line DND39.
The expression of epsilon germline transcripts (epsilon GT) 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 epsilon GT expression in the human B cell line DND39. We show here that the PPAR gamma ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), can suppress epsilon GT expression at 1 microM without inhibiting cell proliferation. A synthetic and PPAR gamma-specific ligand, ciglitazone, also suppressed epsilon GT expression in a dose-dependent manner at concentrations between 10 and 50 microM. Agonists for other PPAR isoforms did not affect epsilon GT expression at concentrations between 0.01 and 10 microM. We also demonstrated that 1 microM 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 epsilon GT expression. Therefore, the suppression of STAT6 phosphorylation by 15d-PGJ(2) is thought to participate in the inhibition of epsilon GT expression. These results suggest that PPAR gamma ligands inhibit IL-4-induced IgE class switching in B lymphocytes.
Miyazaki
Yoshiyuki
Y
Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Laboratory of Food Chemistry, Faculty of Agriculture, Kyushu University, 46-09, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
Tachibana
Hirofumi
H
Yamada
Koji
K
D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D005854:Germ Cells; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology; D008024:Ligands; D010766:Phosphorylation; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007143:Immunoglobulin Heavy Chains; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D013844:Thiazoles; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4; D007073:Immunoglobulin E; D015230:Prostaglandin D2; C039671:ciglitazone