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-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.
Borg
L A
LA
Department of Medical Cell Biology, Uppsala University, Sweden.
Cagliero
E
E
Sandler
S
S
Welsh
N
N
Eizirik
D L
DL
D000199:Actins / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008782:Methylurea Compounds / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013876:Thiophenes / Q000494:pharmacology
D000199:Actins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008782:Methylurea Compounds; D010618:Phenanthrolines; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D013876:Thiophenes; D003609:Dactinomycin; C000486:citiolone; D013482:Superoxide Dismutase; C018275:1,1-dimethylurea