Sandler S, Bendtzen K, Eizirik D L, Sjöholm A, Welsh N
Department of Medical Cell Biology, Uppsala University, Sweden.
Immunol Lett. 1989 Oct;22(4):267-72. doi: 10.1016/0165-2478(89)90164-8.
Interleukin 1 (IL-1) has been suggested to cause the islet B cell destruction occurring during the development of insulin-dependent diabetes mellitus. One mechanism by which B cell loss can be compensated for is via de novo formation of new cells through replication. In the present study the replicatory activity of cells in isolated rat pancreatic islets and in the insulin-producing cell line RINm5F has been assessed by [3H]thymidine incorporation methods after exposure to 1-25 U/ml of human recombinant IL-1 beta (rIL-1 beta). In the rat islets [3H]thymidine incorporation was decreased by 20% 5 h after exposure to 25 U/ml rIL-1 beta. A similar inhibition was also observed in islets exposed to 2.5 and 12.5 U/ml rIL-1 beta. In the RINm5F cells there was a dose-dependent inhibition of the cell replication to approximately 50% of the controls in cells exposed to 25 U/ml rIL-1 beta for 48 h. This was also accompanied by an increased cell death, as measured by trypan blue inclusion (controls 13% and rIL-1 beta treated cells 25%). The insulin content of the RINm5F cells was reduced by about 40% after a 48-h exposure to 25 U/ml rIL-1 beta. When the exposure of the RINm5F cells to rIL-1 beta was decreased to 24 h there was no increased cell death, but a reduced replicatory activity was still observed. rIL-1 beta decreased the cellular content of the polyamines spermidine and spermine.(ABSTRACT TRUNCATED AT 250 WORDS)
白细胞介素1(IL-1)被认为会导致胰岛素依赖型糖尿病发展过程中发生的胰岛B细胞破坏。一种可以补偿B细胞损失的机制是通过复制从头形成新细胞。在本研究中,通过[3H]胸腺嘧啶核苷掺入法,在暴露于1-25 U/ml人重组IL-1β(rIL-1β)后,评估了分离的大鼠胰岛和胰岛素产生细胞系RINm5F中细胞的复制活性。在大鼠胰岛中,暴露于25 U/ml rIL-1β 5小时后,[3H]胸腺嘧啶核苷掺入减少了20%。在暴露于2.5和12.5 U/ml rIL-1β的胰岛中也观察到了类似的抑制作用。在RINm5F细胞中,暴露于25 U/ml rIL-1β 48小时后,细胞复制受到剂量依赖性抑制,降至对照组的约50%。这也伴随着细胞死亡增加,通过台盼蓝摄入法测量(对照组为13%,rIL-1β处理组细胞为25%)。暴露于25 U/ml rIL-1β 48小时后,RINm5F细胞的胰岛素含量降低了约40%。当RINm5F细胞暴露于rIL-1β的时间减少到24小时时,没有细胞死亡增加,但仍观察到复制活性降低。rIL-1β降低了多胺亚精胺和精胺的细胞含量。(摘要截短于250字)