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标题：Suppressive Effects of T-412, a Flavone on Interleukin-4 Production in T Cells
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作者：Mirim Jin ; Sunyoung Park ; Myoung Yun Pyo 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：11
页码：1875-1879
DOI：10.1248/bpb.32.1875
出版社：The Pharmaceutical Society of Japan
摘要：Interleukin (IL)-4 has been suggested as a molecular therapeutic target to prevent and/or treat various allergic diseases and several flavonoids have been suggested as anti-allergic agents suppressing IL-4 production. In an effort to find novel candidates for anti-allergic agents from natural sources, we screened several flavonoids affecting on IL-4 production. In this study, we showed that 7,8,4′-trihydroxyflavone (T-412) significantly decreased IL-4 production both in phorbol 12-myristate 13-acetate (PMA) and ionomycin (PI)-activated EL-4 T cells and concanavalin A (ConA)-activated murine CD4⁺ T cells in a dose- and time-dependent manner. The PI-induced increase of IL-4 mRNA expression was dramatically suppressed by T-412 at 6 h, indicating the suppression is regulated at transcriptional level. T-412 also significantly inhibited IL-4 gene promoter activity in EL-4 T cells transiently transfected with luciferase reporter plasmid containing IL-4 promoter (pGL4.14-IL-4). Western blot analysis of the transcription factors revealed that T-412 suppressed the nuclear expression of nuclear factor of activated T cells (NF-AT)c1, c-Jun and c-Maf, but not c-Fos and nuclear factor kappa B (NF-κB). Our data suggested that T-412 might have potential as a candidate for anti-allergic agent having suppressive effects on IL-4 production in activated T cells by controlling the transcription of IL-4.
关键词：7,8,4′-trihydroxyflavone;flavone;interleukin-4;T cell;anti-allergic agent