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© 2001 by the American Diabetes Association, Inc.
Identification of Novel Cytokine-Induced Genes in Pancreatic ß-Cells by High-Density Oligonucleotide Arrays
1 Gene Expression Unit, Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan, Brussels, Belgium
2 Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Aarhus N, Denmark
Type 1 diabetes is an autoimmune disease resulting from the selective destruction of insulin-producing ß-cells. Cytokines may contribute to pancreatic ß-cell death in type 1 diabetes. ß-cell exposure to interleukin (IL)-1ß induces functional impairment, whereas ß-cell culture for 6–9 days in the presence of IL-1ß and interferon (INF)-
leads to apoptosis. To clarify the mechanisms involved in these effects of cytokines, we studied the general pattern of cytokine-induced gene expression in ß-cells. Primary rat ß-cells were fluorescence-activated cell sorter–purified and exposed for 6 or 24 h to control condition, IL-1ß + INF-, or IL-1ß alone (24 h only). Gene expression profile was analyzed in duplicate by oligonucleotide arrays. Nearly 3,000 transcripts were detected in controls and cytokine-treated ß-cells. Of these, 96 and 147 displayed changes in expression after 6 and 24 h, respectively, of exposure to IL-1ß + INF-, whereas 105 transcripts were modified after a 24-h exposure to IL-1ß. The cytokine-responsive genes were clustered according to their biological functions. The major clusters observed were metabolism, signal transduction, transcription factors, protein synthesis/processing, hormones, and related receptors. These modifications in gene expression may explain some of the cytokine effects in ß-cells, such as decreased protein biosynthesis and insulin release. In addition, there was induction of diverse cytokines and chemokines; this suggests that ß-cells may contribute to mononuclear cell homing during insulitis. Several of the cytokine-induced genes are potentially regulated by the transcription factor NF-
B. Clarification of the function of the identified cytokine-induced gene patterns may unveil some of the mechanisms involved in ß-cell damage and repair in type 1 diabetes.
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