Simvastatin Prevents and Reverses Depigmentation in a Mouse Model of Vitiligo

Agarwal, P. and Rashighi, M. and Essien, K.I. and Richmond, J.M. and Randall, L. and Pazoki-Toroudi, H. and Hunter, C.A. and Harris, J.E. (2015) Simvastatin Prevents and Reverses Depigmentation in a Mouse Model of Vitiligo. Journal of Investigative Dermatology, 135 (4). pp. 1080-1088.

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Abstract

Vitiligo is a common autoimmune disease of the skin that results in disfiguring white spots. There are no Food and Drug Administration (FDA)-approved treatments, and current treatments are time-consuming, expensive, and of low efficacy. We sought to identify new treatments for vitiligo, and first considered repurposed medications because of the availability of safety data and expedited regulatory approval. We previously reported that the IFN-γ-induced chemokine CXCL10 is expressed in lesional skin from vitiligo patients, and that it is critical for the progression and maintenance of depigmentation in our mouse model of vitiligo. We hypothesized that targeting IFN-γ signaling might be an effective new treatment strategy. Activation of signal transducer and activator of transcription 1 (STAT1) is required for IFN-γ signaling and recent studies revealed that simvastatin, an FDA-approved cholesterol-lowering medication, inhibited STAT1 activation in vitro. Therefore, we hypothesized that simvastatin may be an effective treatment for vitiligo. We found that simvastatin both prevented and reversed depigmentation in our mouse model of vitiligo, and reduced the number of infiltrating autoreactive CD8+ T cells in the skin. Treatment of melanocyte-specific, CD8+ T cells in vitro decreased proliferation and IFN-γ production, suggesting additional effects of simvastatin directly on T cells. Based on these data, simvastatin may be a safe, targeted treatment option for patients with vitiligo. © 2015 The Society for Investigative Dermatology.

Item Type: Article
Additional Information: cited By 27
Subjects: WR Dermatology
QV Pharmacology
Depositing User: eprints admin
Date Deposited: 02 Jul 2018 08:01
Last Modified: 09 Dec 2019 06:22
URI: http://eprints.iums.ac.ir/id/eprint/4949

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