Inhibition of interleukin-4 production in activated T cells via down-regulation of NF-AT DNA binding activity by apigenin, a flavonoid present in dietary plants

Apigenin, a flavonoid present in many dietary plants, exhibits anti-allergic activity and inhibits IL-4 production by basophils and mast cells. However, the mechanism by which apigenin suppresses IL-4 production especially in T cells remains unclear. In this study, the effect of apigenin and its underlying mechanism on IL-4 production were investigated in activated T cells. Apigenin significantly inhibited IL-4 production in both EL4 T thymoma cells and primary lymph node cells. Apigenin also inhibited IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 gene promoter constructs, but this inhibitory effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of NF-AT binding sites. In addition, apigenin inhibited NF-AT DNA binding activities, indicating that apigenin may inhibit IL-4 production in T cells via down-regulation of NF-AT DNA binding activity.