Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo.
Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo.
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DOI：
10.1038/jid.2014.529
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发表时间：
2015-04
影响因子：
6.5
通讯作者：
Harris, John E.
中科院分区：
文献类型：
--
作者：
Agarwal, Priti;Rashighi, Mehdi;Essien, Kingsley I.;Richmond, Jillian M.;Randall, Louise;Pazoki-Toroudi, Hamidreza;Hunter, Christopher A.;Harris, John E.
白癜风是一种常见的皮肤自身免疫性疾病，会导致毁容的白斑。目前还没有 FDA 批准的治疗方法，目前的治疗方法耗时、昂贵且疗效低。我们试图寻找白癜风的新疗法，并首先考虑重新调整药物用途，因为可以获得安全数据并加快监管审批。我们之前报道过，IFN-γ诱导的趋化因子CXCL10在白癜风患者的病变皮肤中表达，并且它对于我们的白癜风小鼠模型中色素脱失的进展和维持至关重要。我们假设靶向 IFN-γ 信号传导可能是一种有效的新治疗策略。 STAT1 激活是 IFN-γ 信号传导所必需的，最近的研究表明辛伐他汀（FDA 批准的降胆固醇药物）可在体外抑制 STAT1 激活。因此，我们推测辛伐他汀可能是治疗白癜风的有效方法。我们发现辛伐他汀可以预防和逆转白癜风小鼠模型中的色素脱失，并减少皮肤中浸润的自身反应性 CD8+ T 细胞的数量。体外处理黑素细胞特异性 CD8+ T 细胞可减少增殖和 IFN-γ 产生，表明辛伐他汀直接对 T 细胞产生额外作用。基于这些数据，辛伐他汀可能是白癜风患者安全、有针对性的治疗选择。
Vitiligo is a common autoimmune disease of the skin that results in disfiguring white spots. There are no FDA-approved treatments, and current treatments are time-consuming, expensive, and have 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. STAT1 activation 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.
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影响因子：
30.8
作者：
Dupuis, S;Jouanguy, E;Casanova, JL
通讯作者：
Casanova, JL
影响因子：
4.3
作者：
Mosenson JA;Zloza A;Klarquist J;Barfuss AJ;Guevara-Patino JA;Poole IC
通讯作者：
Poole IC
DOI：
10.1084/jem.188.6.1203
发表时间：
1998-09-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ogg GS;Rod Dunbar P;Romero P;Chen JL;Cerundolo V
通讯作者：
Cerundolo V
影响因子：
15.9
作者：
Dimmeler, S;Aicher, A;Zeiher, AM
通讯作者：
Zeiher, AM
影响因子：
3.6
作者：
Laddha, Naresh C.;Dwivedi, Mitesh;Begum, Rasheedunnisa
通讯作者：
Begum, Rasheedunnisa