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Jieyu Zhang, Hui Fang, Ruoyang Wang, Erle Dang, Man Jiang, Gang Wang
(Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China (mainland))
Med Sci Monit 2017; 23:6049-6056
Calcipotriol ointment has been demonstrated to be a very safe and effective topical drug for psoriasis. This study aims to investigate the effect of calcipotriol on IFN-γ-induced keratin 17 (K17) expression in a human keratinocyte cell line (HaCaT), which is a widely accepted as a mimic in vitro model for psoriasis.
MATERIAL AND METHODS: We used Western blot, immunofluorescence staining, and luciferase reporter system assays to evaluate the expression of K17 and the possible underlying mechanisms.
RESULTS: Administration of IFN-γ (125–1000 U) increased K17 expression in a dose-dependent manner, and 250 U/ml IFN-γ significantly elevated K17 expression. The experimental results showed that calcipotriol at concentrations of 10^–7 M and 10^–5 M suppressed the IFN-γ-induced K17 expression by 58.10% and 70.68%, respectively. Through immunofluorescence staining and luciferase reporter assay, we found that Vitamin D Response Element (VDRE) affected IFN-activated site (Gamma-activated sequence, GAS) function at the transcriptional level and was involved in the inhibition of K17 expression.
CONCLUSIONS: Our data suggest that calcipotriol downregulates IFN-γ-mediated K17 expression in keratinocytes in a dose-dependent manner via VDRE effect GAS function. The inhibitory effect of calcipotriol on K17 expression may be a potential mechanism and function in the treatment psoriasis.