Therapeutic effect of kaempferol on atopic dermatitis by attenuation of T cell activity via interaction with multidrug resistance‐associated protein 1

다국어 초록 (Multilingual Abstract)

Kaempferol is a natural flavonoid widely investigated in various fields due to its antioxidant, anti‐cancer, and anti‐inflammatory activities, but few studies have shown its inhibitory effect on T cell activation. This study examined the therapeutic potential of kaempferol in atopic dermatitis by modulating T cell activation.
Effects of kaempferol on T cell activation and the underlying mechanisms were investigated in Jurkat cells and mouse CD4+ T cells. A model of atopic dermatitis in mice was used to determine its therapeutic potential on T cell‐mediated conditions in vivo. Western blots, RT‐PCR, pulldown assays and ELISA were used, along with histological analysis of skin.
Pretreatment with kaempferol reduced CD69 expression and production of inflammatory cytokines including IL‐2 from activated Jurkat cells and murine CD4+ T cells without cytotoxicity. Pulldown assays revealed that kaempferol physically binds to MRP‐1 in T cells, inhibiting the action of MRP‐1. In activated T cells, kaempferol suppressed JNK phosphorylation and the TAK1‐IKKα mediated NF‐κB pathway. Oral administration of kaempferol to mice showed improved manifestation of atopic dermatitis, a T cell‐mediated condition. Western blot results showed that, as in the in vitro studies, decreased phosphorylation of JNK was associated with down‐regulated MRP‐1 activity in vivo, in the kaempferol‐treated mice in the atopic dermatitis model.
Kaempferol regulates T cell activation by inhibiting MRP‐1 activity in activated T cells, thus showing protective effects against T cell mediated disease in vivo.