INTERLEUKIN-1-BETA INCREASES THE ACTIVITY OF SUPEROXIDE-DISMUTASE IN RAT PANCREATIC-ISLETS

The suppressive effects of interleukin-1-beta (IL-1-beta) on the function of pancreatic islets may be related to induction of gene transcription and protein synthesis. Presently, the effects of human recombinant IL-1-beta (rIL-1-beta) 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-1-beta 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-1-beta. Also, brief exposure of the islets to rIL-1-beta induced an increase in SOD activities. Hence, 12 h after a 1-h exposure of the islets to rIL-1-beta, there was a 1.4-fold increase in the activity of both MnSOD and CuZnSOD. The early induction of SOD by rIL-1-beta 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-1-beta 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-1-beta. 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-1-beta on the pancreatic B-cells, isolated islets were exposed to rIL-1-beta only or to rIL-1-beta plus various free radical scavengers. None of the scavengers, single or in combinations, could counteract the suppressive action of rIL-1-beta on islet insulin secretion. The present data suggest that rIL-1-beta induces increased activity of SOD, in particular MnSOD, in pancreatic islets. This may be due to a direct action of rIL-1-beta that is mediated by an increase in gene transcription.