Jafarian-Tehrani M, Amrani A, Homo-Delarche F, Marquette C, Dardenne M, Haour F
Unité de la Rage, Institut Pasteur, Paris, France.
Endocrinology. 1995 Feb;136(2):609-13. doi: 10.1210/endo.136.2.7835294.
Numerous in vivo and in vitro studies have shown the effects of interleukin-1 (IL-1) on insulin and glucagon secretion. To understand the mechanism of these effects, we performed localization and characterization of IL-1 receptors (IL-1R) in pancreas using a quantitative autoradiography method and recombinant human (rh) [125I]IL-1 alpha as a ligand. Frozen sections of pancreas were studied in control (C3H/He) and nonobese diabetic (NOD) mice (a model of autoimmune type I diabetes). Compared to splenic IL-1R, a very high density of specific IL-1R (> 4-fold that in spleen) was found on the islets of Langerhans in both strains. In C3H/He mice, competition experiments demonstrated the presence of one high affinity binding site (Ki = 3.4 and 3.2 x 10(-10) M; binding capacity, 137 and 122 fmol/mg protein for rhIL-1 alpha and rhIL-1 beta, respectively), comparable to type I IL-1R described on T-lymphocytes. In prediabetic NOD mice, these IL-1R were expressed with the same density, affinity, and specificity as in the control strain. Before the onset of diabetes, the expression of IL-1R protein on the islet cells appears to be entirely normal. In contrast, in diabetic NOD mice, IL-1R are sharply decreased, correlating with the intensity of islet destruction. In conclusion, the localization and high density of IL-1R on the mouse islets of Langerhans complement previous studies showing the presence of messenger RNA for type I IL-1R on the islets of Langerhans. These results support a direct physiological effect of IL-1 on pancreatic hormones, such as insulin and glucagon, and a potential role of IL-1R in the pathogenesis of type I diabetes.
大量的体内和体外研究表明白细胞介素-1（IL-1）对胰岛素和胰高血糖素分泌的影响。为了解这些作用的机制，我们使用定量放射自显影方法以及重组人（rh）[125I]IL-1α作为配体，对胰腺中的IL-1受体（IL-1R）进行了定位和特性分析。在对照（C3H/He）和非肥胖糖尿病（NOD）小鼠（自身免疫性I型糖尿病模型）中研究了胰腺冰冻切片。与脾脏IL-1R相比，在这两种品系的胰岛上均发现了非常高密度的特异性IL-1R（>脾脏中的4倍）。在C3H/He小鼠中，竞争实验证明存在一个高亲和力结合位点（Ki = 3.4和3.2×10(-10) M；结合能力，rhIL-1α和rhIL-1β分别为137和122 fmol/mg蛋白质），与T淋巴细胞上描述的I型IL-1R相当。在糖尿病前期的NOD小鼠中，这些IL-1R以与对照品系相同的密度、亲和力和特异性表达。在糖尿病发作之前，胰岛细胞上IL-1R蛋白的表达似乎完全正常。相反，在糖尿病NOD小鼠中，IL-1R急剧减少，与胰岛破坏的程度相关。总之，IL-1R在小鼠胰岛上的定位和高密度补充了先前显示胰岛上存在I型IL-1R信使RNA的研究。这些结果支持IL-1对胰岛素和胰高血糖素等胰腺激素具有直接生理作用，以及IL-1R在I型糖尿病发病机制中的潜在作用。
