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22 December 2017 : Laboratory Research

Effect of Calcipotriol on IFN-γ-Induced Keratin 17 Expression in Immortalized Human Epidermal Keratinocyte Cells

Jieyu Zhang1ABCDEF, Hui Fang1CE, Ruoyang Wang1BC, Erle Dang1A, Man Jiang1E, Gang Wang1AFG*

DOI: 10.12659/MSM.904850

Med Sci Monit 2017; 23:6049-6056

Abstract

BACKGROUND: 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.

Keywords: Calcitriol, Keratin-17, Psoriasis

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750