Abstract
Background and purpose:
Kaempferol is a natural flavonoid widely investigated in various fields due to its anti-oxidant, 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.
Experimental approach:
For in vitro study, Jurkat cells and mouse CD4+ T cells were used in present study to show whether kamepferol prevents T cell activation and its underlying mechanism. Atopic dermatitis model was used to confirm its therapeutic potential on T cell-mediated disorder in vivo.
Key results:
We explored pre-treatment with kaempferol reduces the CD69 expression and pro-inflammatory cytokines production including IL-2 from activated Jurkat cells and murine CD4+ T cells without cytotoxicity. Pulldown assay revealed kaempferol physically binds to MRP-1 in T cells. We found this interaction leads to the inhibition of MRP-1 activity and it suppresses JNK phosphorylation in activated T cells. Western blot analysis exhibited TAK1-IKKα mediated NFκB pathway is also hindered by kaempferol treatment as previously reported in activated T cells. Oral administration of kaempferol showed improved manifestation of atopic dermatitis, one of T cell-mediated diseases. Western blot results revealed correlation with in vitro model that declined level of phosphorylated JNK is associated with downregulated MRP-1 activity in vivo in kaempferol-treated mice group.
Conclusion and implications:
Kaempferol regulates T cell activation via modulation of MRP-1 activity in activated T cells, showing protective role against T cell mediated disease in vivo.
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