Effect of interferon-gamma and glucose on major histocompatibility complex class I and class II expression by pancreatic beta- and non-beta-cells
Effect of interferon-gamma and glucose on major histocompatibility complex class I and class II expression by pancreatic beta- and non-beta-cells
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DOI：
10.1210/jc.82.7.2329
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发表时间：
1997-07-01
影响因子：
5.8
通讯作者：
Pipeleers, D
中科院分区：
文献类型：
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作者：
Pavlovic, D;VandeWinkel, M;Pipeleers, D
胰岛细胞表达的表面主要组织相容性复合物（MHC）I类和II类被认为是可导致糖尿病的免疫过程的局部启动子或调节子。已知局部释放的细胞因子，特别是干扰素-γ，刺激胰岛细胞的MHC抗原表达。本研究定量了大鼠和人体器官中培养的胰腺β细胞和非β细胞中MHC的表达。干扰素-γ增加了内分泌β细胞和非β细胞以及胰腺导管细胞中的MHC I类表达。细胞因子诱导胰腺β细胞中MHC I类信使核糖核酸水平增加6倍;在葡萄糖水平升高（20 mmol/L而不是6 mmol/L）的情况下，该效应放大2倍。在内分泌β-或非β-细胞中没有观察到MHC II类表达;人，但不是大鼠，导管细胞表现出MHC II类表达，在干扰素-γ的存在下增加。这些数据表明，β-细胞MHC I类表达的增加在糖尿病患者的胰腺中描述可能是由于暴露于局部释放的干扰素-γ和/或高血糖状态后刺激转录。人类胰岛与导管细胞的关联，其中MHC II类表达被干扰素-γ刺激，使得这些细胞成为糖尿病自身免疫过程的潜在参与者。
Surface major histocompatibility complex (MHC) class I and class II expression by pancreatic islet cells is considered a local initiator or regulator of immune processes that can lead to diabetes. Locally released cytokines, in particular interferon-gamma, are known to stimulate MHC antigen expression by islet cells. The present study quantifies MHC expression in cultured pancreatic beta- and non-beta-cells from both rat and human organs. Interferon-gamma increased MHC class I expression in endocrine beta- and non-beta-cells as well as in pancreatic ductal cells. The cytokine induced a 6-fold increase in the MHC class I messenger ribonucleic acid levels in pancreatic beta-cells; this effect was 2-fold amplified in the presence of elevated glucose levels (20 mmol/L instead of 6 mmol/L). No MHC class II expression was observed in endocrine beta- or non-beta-cells; human, but not rat, ductal cells exhibited MHC class II expression that increased in the presence of interferon-gamma.These data indicate that the increase in beta-cell MHC class I expression described in the pancreata of diabetic patients may result from stimulated transcription after exposure to locally released interferon-gamma and/or to a hyperglycemic state. The association of human islets with ductal cells in which MHC class II expression is stimulated by interferon-gamma makes these cells potential participants in the autoimmune process in diabetes.