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

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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-Δ12;14-prostaglandin J2 (15d-PGJ2), 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 50μM. Agonists for other PPAR isoforms did not affect εGT expression at concentrations between 0.01 and 10μM. We also demonstrated that 1μM 15d-PGJ2 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-PGJ2 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.

Original languageEnglish
Pages (from-to)547-552
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume295
Issue number2
DOIs
Publication statusPublished - Jul 30 2002

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Peroxisome Proliferator-Activated Receptors
Immunoglobulin E
B-Lymphocytes
Interleukin-4
Cells
Ligands
Cell Line
STAT6 Transcription Factor
Immunoglobulin Class Switching
Phosphorylation
Lymphocytes
Cell proliferation
Protein Isoforms
Transcription Factors
Cell Proliferation
15-deoxy-delta(12,14)-prostaglandin J2

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "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-Δ12;14-prostaglandin J2 (15d-PGJ2), 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 50μM. Agonists for other PPAR isoforms did not affect εGT expression at concentrations between 0.01 and 10μM. We also demonstrated that 1μM 15d-PGJ2 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-PGJ2 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.",
author = "Yoshiyuki Miyazaki and Hirofumi Tachibana and Koji Yamada",
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T1 - 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

AU - Miyazaki, Yoshiyuki

AU - Tachibana, Hirofumi

AU - Yamada, Koji

PY - 2002/7/30

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N2 - 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-Δ12;14-prostaglandin J2 (15d-PGJ2), 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 50μM. Agonists for other PPAR isoforms did not affect εGT expression at concentrations between 0.01 and 10μM. We also demonstrated that 1μM 15d-PGJ2 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-PGJ2 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.

AB - 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-Δ12;14-prostaglandin J2 (15d-PGJ2), 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 50μM. Agonists for other PPAR isoforms did not affect εGT expression at concentrations between 0.01 and 10μM. We also demonstrated that 1μM 15d-PGJ2 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-PGJ2 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.

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