Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes.
Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes.
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DOI：
10.1136/bmjdrc-2016-000219
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发表时间：
2016
影响因子：
4.1
通讯作者：
POD-V Consortium
中科院分区：
文献类型：
--
作者：
Hodik M;Anagandula M;Fuxe J;Krogvold L;Dahl-Jørgensen K;Hyöty H;Sarmiento L;Frisk G;POD-V Consortium
将人类胰岛肠道病毒（EV）感染与1型糖尿病（T1 D）联系起来的理论之一是胰岛中肥沃区域的发育。这意味着诱导用于病毒复制的适当蛋白质，例如柯萨奇-腺病毒受体（CAR）。本研究的目的是研究CAR在人类胰岛中表达的程度，以及什么条件会改变表达。对来自T1 D患者（n=9个近期发作的T1 D，n=4个长期存在的T1 D）、胰岛自身抗体阳性个体（n=14）和非糖尿病对照（n=24）个体的石蜡包埋的胰腺组织进行CAR的免疫组织化学。还通过逆转录PCR在显微切割的胰岛（n=5）、外分泌组织（n=5）和感染EV或暴露于由EV感染的胰岛细胞产生的趋化因子的分离的胰岛上检测CAR的表达。T1 D患者和自身抗体阳性个体在胰腺中表达CAR的频率增加（p<0.039）。与非糖尿病对照（6/24）相比，CAR染色在来自T1 D患者和自身抗体阳性受试者（15/27）的胰岛中更频繁地检测到（p<0.033）。同样，在来自柯萨奇病毒B（CBV）-1感染的胰岛的在UV处理的培养基中培养的胰岛中，CAR基因的表达与对照相比增加。胰腺组织的激光显微切割显示，胰腺内分泌细胞中的CAR表达比外分泌细胞高10倍。CAR也表达在胰岛中，并且表达水平随着培养时间的推移而降低。CBV-1感染后胰岛CAR表达明显降低（p<0.05）。与此相反，感染埃可病毒6没有影响CAR的表达。CAR在患有T1 D的患者的胰岛中表达，并且CAR的表达水平在暴露于由感染的胰岛产生的促炎细胞因子/趋化因子的受损胰岛中增加。T1 D与胰岛中某些趋化因子/细胞因子水平的增加相关，这可能是T1 D胰岛中CAR表达增加的机制。
One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie–adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets.
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