034 Estradiol plays regulatory roles in an imiquimod-induced murine psoriatic dermatitis through down-regulation of keratinocyte activation

It has been reported that psoriasis symptoms have improved during pregnancy, while deteriorated after menopause, suggesting protective roles of estradiol in the development of psoriasis. In addition, the severity of psoriasis tends to be higher in male than in female in Asian countries. However, the precise mechanisms of estradiol regulating the development of psoriasis remain largely unclear. To evaluate the potential roles of estradiol on the development of psoriasis, we firstly subjected ovariectomized-female mice to an imiquimod-induced murine psoriasis model with or without systemic estradiol administration. Mice treated with estradiol exhibited significantly attenuated dermal edema, inflammatory cell infiltration and epidermal hyperplasia when compared to vehicle-treated mice. The mRNA expressions of keratinocyte-derived cytokines (such as IL-24 and CXCL1) and dendritic cell (DC)-derived cytokines (such as IL-23p19 and IL-12/23p40) after imiquimod treatment were significantly impaired by treatment with estradiol, suggesting that estradiol exerts regulatory roles on psoriatic dermatitis by suppressing cytokine expression from keratinocytes and/or DCs. In vitro, estradiol directly down-regulated the mRNA induction of various cytokines (including IL-24 and CXCL1) in primary murine keratinocytes and normal human epidermal keratinocytes stimulated with aldara and TNFα, respectively. On the other hand, estradiol did not suppress the induction of IL-23p19 and IL-12/23p40 in imiquimod-stimulated bone marrow-derived DCs. We also confirmed that the expression of estrogen receptor α and β in keratinocytes and DCs using flow cytometry analysis. Taken together, these results suggest that estradiol plays protective roles in imiquimod-induced murine psoriatic dermatitis via inhibiting the production of inflammatory mediators by keratinocytes.