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.
Jin
Mirim
M
Lab of Pathology, College of Oriental Medicine, Daejeon University, Daejeon University; Daejeon 300-716, Korea.
Park
Sunyoung
S
Pyo
Myoung Yun
MY
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D047309:Flavones / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D017931:DNA Primers; D047309:Flavones; D012333:RNA, Messenger; D015847:Interleukin-4; C055505:norwogonin