INHIBITION BY DEXAMETHASONE OF RETINOIC ACID-INDUCED ENHANCEMENT OF LEUKOTRIENE C-4 SYNTHESIS IN RAT BASOPHILIC LEUKEMIA-1 CELLS

We investigated inhibitory actions of dexamethasone (DEX) on retinoic acid (RA)-induced enhancement of leukotriene C4 (LTC4) synthesis in ra t basophilic leukemia-1 (RBL-1) cells. Cultured cells were preincubate d with RA for 16 h with or without DEX, and generation of LTC4 was mea sured by high performance liquid chromatography in cell-free and intac t cell systems. RA (0.1 mug/ml) significantly potentiated calcium iono phore-stimulated production of LTC4 synthesis. DEX inhibited the RA-in duced enhancement of LTC4 synthesis by up to approximately 95 % in int act cells when stimulated with calcium ionophore. RA-induced LTC4 synt hase activity, which was determined by enzyme assay, was also inhibite d by DEX by 65 % in a cell-free system. This discrepancy of inhibition between the intact and cell-free systems was due to a partial inhibit ion of phospholipase A2 activity by DEX in the intact cells. These res ults indicate that the production of LTC4 is predominantly regulated a t a level of LTC4 synthase. The induction of new LTC4 Synthase activit y by RA and inhibition of the RA-induced activity by DEX are important regulatory mechanisms of LTC4 synthesis.