Fisetin에 의한 비만세포 Th2 사이토카인 발현 하향 조절

Abstract

Mast cells play pivotal pathologic roles in allergic disease involving T helper 2 (Th2) cytokine such as interleukin (IL)-4 and IL-13. Fisetin has been known as an anti-allergic agent having inhibitory effects on the IL-4 and IL-13 gene expressions in inflammatory immune cells. However, its molecular mechanisms for suppressive effects of fisetin on IL-4 and IL-13 in activated mast cells have been incompletely elucidated. In this study we found that fisetin significantly inhibited the phorbol 12-myristate 13-acetate (PMA) and ionomycin (PI)-induced production of IL-4 and IL-13 in mast cells. The levels of mRNA were dramatically decreased by fisetin, indicating the suppression might be regulated at the transcriptional levels. Western blot analysis of the nuclear expression of various transcription factors involved in the promoter activation indicated that suppression of c-Fos was prominent together with significant down-regulation of nuclear factor of activated T-cell (NF-AT) and NF-κB, but not c-Jun. Furthermore, the nuclear expression of GATA binding protein 2 (GATA-2) transcription factor was significantly down-regulated by fisetin. Taken together, our study indicated fisetin has suppressive effects on IL-4 and IL-13 gene expression through the regulation of selective transcription factors.