Ankarcrona M, Dypbukt J M, Brüne B, Nicotera P
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Exp Cell Res. 1994 Jul;213(1):172-7. doi: 10.1006/excr.1994.1187.
Cytokine production during type I insulin-dependent diabetes mellitus has been linked to alterations in beta-cell function such as inhibition of glucose-stimulated insulin secretion. This and other adverse effects of cytokines, including interleukin-1 beta (IL-1 beta) involve the induction of nitric oxide synthase, with production of nitric oxide. Here, we show that IL-1 beta induces apoptosis in a pancreatic beta-cell line, RINm5F cells. Cells treated with IL-1 beta underwent DNA fragmentation, nuclear condensation, and apoptotic body formation. The production of nitric oxide preceded the appearance of these typical features of apoptosis. Inhibition of the nitric oxide synthase activity by NG-monomethyl-L-arginine prevented IL-1 beta-induced nitric oxide generation and apoptotic cell killing. These results show that--besides the known alterations in beta-cell function--IL-1 beta-induced nitric oxide production activates the cell death program.
在I型胰岛素依赖型糖尿病期间，细胞因子的产生与β细胞功能的改变有关，如抑制葡萄糖刺激的胰岛素分泌。细胞因子的这种及其他不良反应，包括白细胞介素-1β（IL-1β），都涉及一氧化氮合酶的诱导及一氧化氮的产生。在此，我们表明IL-1β可诱导胰腺β细胞系RINm5F细胞凋亡。用IL-1β处理的细胞发生DNA片段化、核浓缩和凋亡小体形成。一氧化氮的产生先于这些典型凋亡特征的出现。NG-单甲基-L-精氨酸对一氧化氮合酶活性的抑制可阻止IL-1β诱导的一氧化氮生成及凋亡细胞杀伤。这些结果表明，除了已知的β细胞功能改变外，IL-1β诱导的一氧化氮产生还激活了细胞死亡程序。
