Effects of Topical Application of Betamethasone on Imiquimod-induced Psoriasis-like Skin Inflammation in Mice.

Abstract

Psoriasis is a chronic inflammatory skin disease mediated by dysregulated auto-reactive immune system. In this study, in order to confirm and further extend the pharmacological basis of topical steroids in psoriasis therapy, we investigated the effect of betamethasone ointment on imiquimod (IMQ)-induced skin inflammation in mice. In BALB/c mice, topical IMQ at the dose of 250 µg each on both sides of the ear induced marked psoriasis-like skin inflammation within 5 days. The same dose of IMQ produced only slight to moderate skin inflammation even on Day 7 in CB-17 scid mice. IMQ-induced skin inflammation was associated with increased levels of mRNA transcripts expression of signature cytokines of T helper (Th)1/Th17 cells, i.e., interferon-γ, interleukin (IL)-17 and IL-22 on Day 5. In addition, levels of mRNA expression of the markers of keratinocytes, i.e., IL-1β, S100A8, and S100A9, were dramatically elevated in IMQ-treated mice. The IMQ-induced changes in cytokine expression were significantly suppressed by topical treatment with betamethasone ointment. IMQ failed to produce significant changes in the mRNA levels of tumor necrosis factor-α as a marker of macrophages and NK1.2 as a marker of natural killer cells and natural killer T cells. In contrast, mRNA level of a Th2 cytokine IL-13 was significantly decreased by IMQ treatment and further suppressed by betamethasone. These findings provide the first pharmacological evidence that the topical application of betamethasone prevents IMQ-induced psoriasis-like skin inflammation in mice by inhibiting gene expressions of various cytokines related to Th1 cells, Th17 cells and keratinocytes.