Identification of IL-1 beta-induced messenger RNAs in rat pancreatic beta cells by differential display of messenger RNA

Aims/hypothesis. Interleukin-1 beta is a putative mediator of pancreatic be ta-cell dysfunction and damage in Type I (insulin-dependent) diabetes melli tus. To better understand the molecular mechanisms involved in IL-1 beta ef fects, we carried out a differential display of mRNA by RT-PCR to identify novel cytokine-regulated genes. Methods. Fluorescence activated cell sorting-purified rat pancreatic beta-c ells were exposed for 6 or 24 h to IL-1 beta. Differentially expressed cDNA bands were cloned and then identified by comparing their sequences with da ta from the GenBank. Differential gene expression was confirmed by RT-PCR u sing specific primers. Results. Interleukin-1 beta increased the expression of adenine nucleotide translocator-l, phospholipase D-1 and cytokine-induced neutrophil chemoattr actant-1 and decreased expression of the protein tyrosine phosphatase-like protein IA-2. Interleukin-1 beta-induced differential expression of these g enes in beta cells was confirmed by RT-PCR. In additional studies, IL-1 bet a was shown to induce chemokines other than cytokine-induced neutrophil che moattractant-1, including cytokine-induced neutrophil chemoattractant-3 and monocyte chemotactic protein-1. Conclusion/interpretation. Our observations indicate that IL-1 beta modifie s the expression of several genes in pancreatic beta cells. These genes may affect both function, viability and beta-cell recognition by the immune sy stem. Functional characterization of the mRNAs which have been identified c ould facilitate a better understanding of the mechanisms leading to beta-ce ll destruction in Type I diabetes.