Antiviral Effect of Nicotinamide on Enterovirus-Infected Human Islets In Vitro: Effect on Virus Replication and Chemokine Secretion
Antiviral Effect of Nicotinamide on Enterovirus-Infected Human Islets In Vitro: Effect on Virus Replication and Chemokine Secretion
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DOI：
10.1002/jmv.21476
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发表时间：
2009-06-01
影响因子：
12.7
通讯作者：
Frisk, Gun
中科院分区：
文献类型：
--
作者：
Moell, Annika;Skog, Oskar;Frisk, Gun
1型糖尿病是一种慢性疾病，其特征在于胰腺中产生胰岛素的细胞的选择性破坏。肠道病毒（EV）是启动这种破坏的主要候选者，并且EV感染诱导了几种炎性趋化因子。烟酰胺已被证明可以保护分离的人胰岛，并调节趋化因子的表达。本研究的目的是评估烟酰胺对EV复制和EV诱导的趋化因子分泌以及人胰岛细胞溶解的影响。使用两种EV菌株在体外感染人胰岛，一种是从1型糖尿病发作时的儿童中分离的裂解型（Adrian），另一种是非裂解型（VD 2921）。在感染后的不同时间点测量趋化因子IP-10和MCP-1的分泌、病毒复制和病毒诱导的细胞病变效应（CPE）。向培养基中添加烟酰胺可显著降低病毒复制和病毒诱导的胰岛破坏/CPE。与模拟感染的对照胰岛相比，当在感染后2-3天和5-7天测量时，两种EV菌株增加了IP-10和MCP-1的分泌。IP-10不产生未感染的孤立的胰岛，而MCP-1的基础分泌检测。有趣的是，添加烟酰胺完全阻断（Adrian）或显著降低（VD 2921）病毒诱导的IP-10分泌。在烟酰胺存在下，感染和未感染胰岛的MCP-1分泌也减少。报告的烟酰胺抗病毒作用可能对治疗/预防病毒和免疫介导的疾病有意义。此外，这项研究强调了病毒诱导的1型糖尿病的可能机制，通过诱导MCP-1和IP-10在胰岛。J. Med. Virol. 81：1082-1087，2009. (c)2009 Wiley-Liss，Inc.
Type 1 diabetes is a chronic disease characterized by the selective destruction of insulin-producing cells in the pancreas. Enterovirus (EV) is the prime candidate to initiate this destruction and several inflammatory chemokines are induced by EV infection. Nicotinamide has been shown to protect isolated human islets, and to modulate chemokine expression. The aim of this study was to evaluate the effect of nicotinamide on EV replication and EV-induced chemokine secretion and cytolysis of human islets. Two EV strains were used to infect human islets in vitro, one lytic (Adrian) isolated from a child at onset of type 1 diabetes, and one non-lytic (VD2921). Secretion of the chemokines IP-10 and MCP-1, viral replication, and virus-induced cytopathic effect (CPE), were measured at different time points post-infection. Addition of nicotinamide to the culture medium reduced viral replication and virus-induced islet destruction/CPE, significantly. Both EV strains increased secretion of IP-10 and MCP-1, when measured days 2-3, and days 5-7 post infection, compared to mock-infected control islets. IP-10 was not produced by uninfected isolated islets, whereas a basal secretion of MCP-1 was detected. Interestingly, addition of nicotinamide blocked completely (Adrian), or reduced significantly (VD2921), the virus-induced secretion of IP-10. Secretion of MCP-1 was also reduced in the presence of nicotinamide, from infected and uninfected islets. The reported antiviral effects of nicotinamide could have implications for the treatment/prevention of virus- and immune-mediated disease. Also, this study highlights a possible mechanism of virus-induced type 1 diabetes through the induction of MCP-1 and IP-10 in pancreatic islets. J. Med. Virol. 81:1082-1087, 2009. (c) 2009 Wiley-Liss, Inc.