慢性接触皮膚炎モデルマウスにおけるNrf2-ARE経路活性化物質の抗炎症作用機序

抄録

Contact hypersensitivity is an inflammatory skin disease with pruritus and pain. Previously, we isolated 2',3'-dihydroxy-4',6'-dimethoxychalcone (DDC) from green perilla as an activator of Nrf2-ARE pathway, and reported that DDC suppressed the increases in auricular thickness. In this study, we examined the effect of DDC on inducible nitric oxide synthase (iNOS) expression and that of a NOS inhibitor on auricular thickness and scratching behavior in chronic contact hypersensitivity (cCHS) model mice.

cCHS was evoked by applying 1% picryl chloride (PCl) on the right auricle of male ICR mice aged 4 weeks. The auricle was sensitized with PCl (Day -7). After seven days (Day 0), the auricle was exposed to PCl every 2 days for 12 days. Drug administration was performed 2 hours after PCl treatment from Day 6. The auricular thickness was measured with a thickness gauge. The number of scratching was counted for 10 min. The expression of iNOS was investigated by Western blotting and immunohistochemical staining.

The increase in the auricular thickness induced by PCl was suppressed in an administration time-dependent manner of DDC. The expression level of iNOS after PCl treatment in the auricle increased with the swelling of auricle. After DDC administration, iNOS expression level was decreased. Administration of a NOS inhibitor suppressed the increase in the auricular thickness and scratching behavior in a dose-dependent manner.

These results suggest that inhibition of iNOS-derived NO production has an important role in the anti-inflammatory mechanism of DDC in cCHS mice.