Berg A-K, Korsgren O, Frisk G
Department of Women's and Children's Health, Uppsala University, Akademiska Sjukhuset, ing 95/96, SE-751 85 Uppsala, Sweden.
Diabetologia. 2006 Nov;49(11):2697-703. doi: 10.1007/s00125-006-0429-7. Epub 2006 Sep 13.
AIMS/HYPOTHESIS: Enterovirus infections have long been suspected to be environmental factors that may cause type 1 diabetes, but the pathways leading from infection to beta cell destruction are still unknown. We therefore examined whether enterovirus infection of human islets leads to upregulation of interferon-gamma-inducible protein (IP-10, now known as chemokine [C-X-C motif] ligand 10 [CXCL10]), a chemokine important for the induction of insulitis.
Isolated human islets were infected with three different strains of Coxsackie B4 virus. IP-10 expression and secretion from the infected human islets were then measured using RT-PCR and ELISA at several time points.
IP-10 was clearly upregulated in and secreted from human islets during enterovirus infection. This was demonstrated with three different strains of Coxsackie B4 virus, two of which are lytic to islets and one which is non-lytic and can establish a persistent infection in human islets.
CONCLUSIONS/INTERPRETATION: We propose that enterovirus-induced upregulation of IP-10 during infection of the islets in vivo is the first step towards destructive insulitis. Our findings support the idea that enterovirus infection triggers immune-mediated beta cell destruction, and for the first time suggest a possible mechanism behind enterovirus-induced diabetes.
目的/假设：长期以来，人们一直怀疑肠道病毒感染是可能导致1型糖尿病的环境因素，但从感染到β细胞破坏的途径仍不清楚。因此，我们研究了人胰岛的肠道病毒感染是否会导致干扰素-γ诱导蛋白（IP-10，现称为趋化因子[C-X-C基序]配体10 [CXCL10]）上调，这是一种对诱导胰岛炎很重要的趋化因子。
将分离的人胰岛用三种不同毒株的柯萨奇B4病毒感染。然后在几个时间点使用逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）测量受感染人胰岛中IP-10的表达和分泌。
在肠道病毒感染期间，人胰岛中的IP-10明显上调并分泌。这在三种不同毒株的柯萨奇B4病毒中得到证实，其中两种毒株对胰岛具有溶细胞性，另一种毒株不具有溶细胞性且可在人胰岛中建立持续感染。
结论/解读：我们提出，体内胰岛感染期间肠道病毒诱导的IP-10上调是导致破坏性胰岛炎的第一步。我们的研究结果支持肠道病毒感染引发免疫介导的β细胞破坏这一观点，并首次提出肠道病毒诱导糖尿病背后的一种可能机制。
