POSTTRANSCRIPTIONAL REGULATION OF LTC4 SYNTHASE ACTIVITY BY RETINOIC ACID IN RAT BASOPHILIC LEUKEMIA-CELLS

Calcium ionophore-stimulated production of leukotriene (LT) C-4 was en hanced by 16-to 26-h incubation with retinoic acid (RA) in rat basophi lic leukemia-1 cells. Production of LTC4 by enzyme assay using cell ly sates as the enzyme source and LTA(4) as the substrate was also enhanc ed by RA-treatment. Production of LTB4 was not enhanced under these tw o experimental conditions, suggesting the preferential activation of L TC4 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 syntha se was not affected by the exposure to RA, DEX or CSA. These results i ndicate that RA-induced enhancement of LTC4 production and its inhibit ion by DEX and CSA was determined by post-transcriptional regulation o f LTC4 synthase. (C) 1997 Elsevier Science B.V.