Post-transcriptional regulation of LTC4 synthase activity by retinoic acid in rat basophilic leukemia cells

Abstract

Calcium ionophore-stimulated production of leukotriene (LT) C4 was enhanced by 16- to 26-h incubation with retinoic acid (RA) in rat basophilic leukemia-1 cells. Production of LTC4 by enzyme assay using cell lysates as the enzyme source and LTA4 as the substrate was also enhanced by RA-treatment. Production of LTB4 was not enhanced under these two experimental conditions, suggesting the preferential activation of LTC4 synthase activity. The RA-induced enhancement of LTC4 synthesis by the cells was suppressed by co-incubation with dexamethasone (DEX) or cyclosporine A (CSA). However, the expression of mRNA for LTC4 synthase was not affected by the exposure to RA, DEX or CSA. These results indicate that RA-induced enhancement of LTC4 production and its inhibition by DEX and CSA was determined by post-transcriptional regulation of LTC4 synthase.