INTERLEUKIN-1-BETA REGULATES THE EXPRESSION OF A LEUKOCYTE TYPE OF 12-LIPOXYGENASE IN RAT ISLETS AND RIN M5F CELLS

The leukocyte type of 12-lipoxygenase (12-LO) may play a role in infla mmatory reactions in many cell types through the conversion of arachid onic acid to proinflammatory eicosanoids that include 12-hydroperoxyei cosatetraenoic acid and 12-hydroeicosatetraenoic acid. Previous studie s demonstrating the presence of a functional 12-LO pathway in rat and human pancreatic beta-cells plus the recent cloning of a rat leukocyte type of 12-LO allowed us to evaluate whether inflammatory cytokines s uch as interleukin-1 beta (IL-1 beta) can regulate the beta-cell 12-LO enzyme pathway, thus providing a potential link between the cytotoxic effects of cytokines on pancreatic beta-cells and the proinflammatory effects of 12-LO products. We demonstrate that IL-1 beta induces 12-L O protein and messenger RNA (mRNA) expression in RIN m5F cells and 12- LO mRNA expression in rat islets. RIN m5F cells treated for 16 h with IL-1 beta (25, 50, and 100 ng/liter) showed a maximal 2-fold increase in the expression of a leukocyte form of 12-LO demonstrated by Western blots. A concomitant increase in 12-LO mRNA expression was seen at th is time point using a highly sensitive competitive polymerase chain re action assay. The increase in mRNA and protein expression was preceded by increased 12-LO pathway activity measured by a RIA for 12-S-HETE. Separate experiments using purified Sprague-Dawley rat islets also sho wed increased expression of 12-LO mRNA and enzyme activity in response to IL-1 beta. These results demonstrate that IL-1 beta can upregulate 12-LO expression and activity in rat beta-cells.