Interleukin-1β increases the activity of superoxide dismutase in rat pancreatic islets

Abstract

The suppressive effects of interleukin-1β (IL-1β) on the function of pancreatic islets may be related to induction of gene transcription and protein synthesis. Presently, the effects of human recombinant IL-1β (rIL-1β) on the activities of superoxide dismutase (SOD) and the expression of corresponding genes were studied in rat pancreatic islets. Islets that were exposed to rIL-1β for 48 h showed a 2.6-fold greater activity of mitochondrial manganese containing SOD (MnSOD) than control islets. The cytosolic copper- and zinc-containing SOD (CuZnSOD) was, however, less affected by rIL-1β. Also, brief exposure of the islets to rIL-1β induced an increase in SOD activities. Hence, 12 h after a 1-h exposure of the islets to rIL-1β, there was a 1.4-fold increase in the activity of both MnSOD and CuZnSOD. The early induction of SOD by rIL-1β was inhibited by an interleukin-1 receptor antagonist protein and actinomycin-D, which is a blocker of gene transcription. This suggests that the effects of rIL-1β on the islet SOD activities are dependent on binding to membrane receptors and activation of gene transcription. Northern blot analysis showed a 4-fold increase in islet MnSOD mRNA content after a 90-min incubation and a 10-fold increase after a 180-min incubation with rIL-1β. Thus, the enhanced MnSOD activity in the islets reflects increased gene expression. To evaluate a possible role for free oxygen radicals as mediators of the early action of rIL-1β on the pancreatic B-cells, isolated islets were exposed to rIL-1β only or to rIL-1β plus various free radical scavengers. None of the scavengers, single or in combinations, could counteract the suppressive action of rIL-1β on islet insulin secretion. The present data suggest that rIL-1β induces increased activity of SOD, in particular MnSOD, in pancreatic islets. This may be due to a direct action of rIL-1β that is mediated by an increase in gene transcription.