triptolide as a potential aryl hydrocarbon receptor antagonist: Identification of antagonist in human T cells and keratinocytes

Triptolide is the main component of extracts of the medicinal plant Tripterygium wilfordii Hook F. and used for systemic treatment of autoimmune disorders. The mechanism of action of triptolide involves the inhibition of differentiation of murine CD4+ T cells into Th17 cells, decreased transcription of IL-17 mRNA. In a CD4+ T-cell line of mice AhR expression is restricted to the Th17 cell subset and its binding to agonists results in the production of the Th17 cytokines. Our study showed that in naïve T cells differentiated Th17-cells the addition of triptolide significantly decreased production of IFN-¿, IL-17A and IL-22 in a dose-dependent manner. Quantitive PCR demonstrated a significant down-regulation of IFN-¿, IL-17A and IL-22 mRNA expression by triptolide in human T cells and potently down-regulated FICZ-induced cytochrome P450 mRNA expression in both keratikocytes and T cells. In conclusion, triptolide was able to potently down-regulate AhR-mediated gene induction and protein expression. These data suggest that triptolide may serve as an AhR-antagonist. The reported anti-inflammatory and immune-suppressive effects of triptolide may be linked to its AhR-antagonistic effect.