Faculty Collaboration Database

Evidence for the presence of type I IL-1 receptors on beta-cells of islets of Langerhans. Biochim Biophys Acta 1997 Oct 24;1361(3):313-20

Date

12/31/1997

Pubmed ID

9375806

DOI

10.1016/s0925-4439(97)00039-2

Scopus ID

2-s2.0-0030667121 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

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.

Author List

Scarim AL, Arnush M, Hill JR, Marshall CA, Baldwin A, McDaniel ML, Corbett JA

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line
Flow Cytometry
Insulin
Insulin Antagonists
Interleukin 1 Receptor Antagonist Protein
Islets of Langerhans
Male
Rats
Rats, Sprague-Dawley
Receptors, Interleukin-1
Sialoglycoproteins