Phenylmethimazole suppresses dsRNA-induced cytotoxicity and inflammatory cytokines in murine pancreatic beta cells and blocks viral acceleration of type 1 diabetes in NOD mice.
Phenylmethimazole suppresses dsRNA-induced cytotoxicity and inflammatory cytokines in murine pancreatic beta cells and blocks viral acceleration of type 1 diabetes in NOD mice.
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苯甲咪唑抑制鼠胰腺β细胞中DSRNA诱导的细胞毒性和炎症细胞因子，并阻止NOD小鼠中1型糖尿病的病毒加速。
DOI：
10.3390/molecules18043841
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发表时间：
2013-03-27
期刊：
影响因子：
--
通讯作者：
Schwartz FL
中科院分区：
文献类型：
--
作者：
McCall KD;Schmerr MJ;Thuma JR;James CB;Courreges MC;Benencia F;Malgor R;Schwartz FL
越来越多的证据支持病毒在1型糖尿病(T1 DM)发病机制中的作用。病毒dsRNA激活dsRNA传感通路，诱导炎性细胞因子和趋化因子的产生，从而触发β细胞凋亡、胰岛炎症和自身免疫介导的β细胞破坏。本研究旨在评估和描述苯并咪唑(C10)的潜在保护作用，该小分子阻断dsRNA介导的信号转导，阻止dsRNA激活β细胞凋亡和在T1 DM发病机制中重要的炎症途径。我们首先研究了C10对体外培养的dsRNA处理的胰岛细胞的生物学效应。应用细胞活力分析、实时定量聚合酶链式反应和ELISAs检测C10对双链RNA诱导的小鼠胰岛β细胞的细胞毒作用和细胞因子/趋化因子产生的影响。我们发现C10能显著降低dsRNA诱导的β细胞毒作用以及参与T1 DM发病的细胞因子和趋化因子的上调，这促使我们评估C10对NOD小鼠T1 DM病毒加速的作用。C10能显著抑制NOD小鼠T1 DM的病毒加速反应。这些发现表明，C10(1)具有新的β细胞保护活性，可能对T1 DM具有潜在的临床意义；(2)C10(2)可能是更好地了解dsRNA介导的反应在T1 DM发病机制中所起作用的有用工具。
Accumulating evidence supports a role for viruses in the pathogenesis of type 1 diabetes mellitus (T1DM). Activation of dsRNA-sensing pathways by viral dsRNA induces the production of inflammatory cytokines and chemokines that trigger beta cell apoptosis, insulitis, and autoimmune-mediated beta cell destruction. This study was designed to evaluate and describe potential protective effects of phenylmethimazole (C10), a small molecule which blocks dsRNA-mediated signaling, on preventing dsRNA activation of beta cell apoptosis and the inflammatory pathways important in the pathogenesis of T1DM. We first investigated the biological effects of C10, on dsRNA-treated pancreatic beta cells in culture. Cell viability assays, quantitative real-time PCR, and ELISAs were utilized to evaluate the effects of C10 on dsRNA-induced beta cell cytotoxicity and cytokine/chemokine production in murine pancreatic beta cells in culture. We found that C10 significantly impairs dsRNA-induced beta cell cytotoxicity and up-regulation of cytokines and chemokines involved in the pathogenesis of T1DM, which prompted us to evaluate C10 effects on viral acceleration of T1DM in NOD mice. C10 significantly inhibited viral acceleration of T1DM in NOD mice. These findings demonstrate that C10 (1) possesses novel beta cell protective activity which may have potential clinical relevance in T1DM and (2) may be a useful tool in achieving a better understanding of the role that dsRNA-mediated responses play in the pathogenesis of T1DM.
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影响因子：
4.4
作者：
Alba, A;Puertas, MC;Vives-Pi, M
通讯作者：
Vives-Pi, M
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4.4
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影响因子：
5.4
作者：
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通讯作者：
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