Evidence for the presence of type I IL-1 receptors on beta-cells of islets of Langerhans.
The cytokine interleukin-1beta (IL-1beta) has been shown to inhibit insulin secretion and destroy pancreatic islets by a mechanism that involves the expression of inducible nitric oxide synthase (iNOS), and the production of nitric oxide (NO). Insulin containing beta-cells, selectively destroyed during the development of autoimmune diabetes, appear to be the islet cellular source of iNOS following treatment with IL-1beta. In this study we have evaluated the presence of type I IL-1 signaling receptors on purified pancreatic beta-cells. We show that the interleukin-1 receptor antagonist protein (IRAP) prevents IL-1beta-induced nitrite formation and IL-1beta-induced inhibition of insulin secretion by isolated islets and primary beta-cells purified by fluorescence-activated cell sorting (FACS). The protective effects of IRAP correlate with an inhibition of IL-1beta-induced iNOS expression by islets and FACS purified beta-cells. To provide direct evidence to support beta-cell expression of IL-1 type I signaling receptors, we show that antiserum specific for the type I IL-1 receptor neutralizes IL-1beta-induced nitrite formation by RINm5F cells, and that RINm5F cells express the type I IL-1 receptor at the protein level. Using reverse transcriptase-polymerase chain reaction (RT-PCR), the expression of type I IL-1 signaling receptors by FACS purified beta-cells and not alpha-cells is demonstrated. These results provide direct support for the expression of type I IL-1 receptors by primary pancreatic beta-cells, the cell type selectively destroyed during the development of autoimmune diabetes.
Scarim
A L
AL
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, MO 63104, USA. scarimal@wpogate.slu.edu
Arnush
M
M
Hill
J R
JR
Marshall
C A
CA
Baldwin
A
A
McDaniel
M L
ML
Corbett
J A
JA
D000818:Animals; D002460:Cell Line; D005434:Flow Cytometry; D007328:Insulin / Q000378:metabolism; D007329:Insulin Antagonists / Q000494:pharmacology; D000078790:Insulin Secretion; D053590:Interleukin 1 Receptor Antagonist Protein; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000494:pharmacology
D007328:Insulin; D007329:Insulin Antagonists; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins