An interleukin-1 receptor antagonist protein protects insulin-producing beta cells against suppressive effects of interleukin-1 beta.
The cytokine interleukin-1 beta may have an important role in the autoimmune mediated damage of pancreatic Beta cells in insulin-dependent diabetes mellitus. In the present study we have investigated the effects of an interleukin-1 receptor antagonist protein, a blocker of the type I interleukin-1 receptor, on the suppressive actions of recombinant interleukin-1 beta on insulin-producing cells. Brief exposure (1-2 h) of rat and mouse pancreatic islets to 10 ng/ml recombinant interleukin-1 beta induced an 70-80% inhibition of insulin response to glucose after 12 h. These effects were completely counteracted by co-incubation with 100 ng/ml interleukin-1 receptor antagonist protein. When rat islets were cultured for 48 h in the presence of recombinant interleukin-1 beta (5 ng/ml) higher concentrations of interleukin-1 receptor antagonist protein (5000 ng/ml) were required to protect Beta-cell function. Interleukin-1 receptor antagonist protein also counteracted the inhibitory effects of recombinant interleukin-1 beta on the growth of the rat insulinoma cell line RINm5F. These data suggest that interleukin-1 receptor antagonist protein can protect insulin-producing cells from the deleterious effects of recombinant interleukin-1 beta, and that these cells possess type I interleukin-1 receptors.
Eizirik
D L
DL
Department of Medical Cell/Biology, Uppsala University, Sweden.
Tracey
D E
DE
Bendtzen
K
K
Sandler
S
S
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005947:Glucose / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
C507764:Il1rn protein, mouse; D007328:Insulin; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011506:Proteins; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D005947:Glucose