Miyazaki Yoshiyuki, Tachibana Hirofumi, Yamada Koji
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.
Biochem Biophys Res Commun. 2002 Jul 12;295(2):547-52. doi: 10.1016/s0006-291x(02)00709-x.
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.
白细胞介素（IL）-4刺激诱导的ε种系转录本（εGT）的表达对于IgE定向类别转换的进展至关重要。在本研究中，我们检测了各种配体结合过氧化物酶体增殖物激活受体（PPARs）的能力以及它们对人B细胞系DND39中IL-4诱导的εGT表达的影响。我们在此表明，PPARγ配体15-脱氧-Δ（12,14）-前列腺素J2（15d-PGJ2）在1μM时可抑制εGT表达，而不抑制细胞增殖。一种合成的PPARγ特异性配体吡格列酮在10至50μM的浓度范围内也以剂量依赖的方式抑制εGT表达。其他PPAR亚型的激动剂在0.01至10μM的浓度范围内不影响εGT表达。我们还证明，1μM的15d-PGJ2能够抑制IL-4诱导的信号转导和转录激活因子6（STAT6）的磷酸化，STAT6是εGT表达所必需的转录因子。因此，15d-PGJ2对STAT6磷酸化的抑制作用被认为参与了对εGT表达的抑制。这些结果表明，PPARγ配体抑制B淋巴细胞中IL-4诱导的IgE类别转换。
