Mc. Chen et al., Identification of IL-1 beta-induced messenger RNAs in rat pancreatic beta cells by differential display of messenger RNA, DIABETOLOG, 42(10), 1999, pp. 1199-1203
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.