Suppressive effects of T-412, a flavone on interleukin-4 production in T cells.

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-kappaB). 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.