Inhibition by dexamethasone of retinoic acid-induced enhancement of leukotriene C4 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 rat basophilic leukemia-1 (RBL-1) cells. Cultured cells were preincubated with RA for 16 h with or without DEX, and generation of LTC4 was measured by high performance liquid chromatography in cell-free and intact cell systems. RA (0.1 microgram/ml) significantly potentiated calcium ionophore-stimulated production of LTC4 synthesis. DEX inhibited the RA-induced enhancement of LTC4 synthesis by up to approximately 95% in intact cells when stimulated with calcium ionophore. RA-induced LTC4 synthase activity, which was determined by enzyme assay, was also inhibited 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 inhibition of phospholipase A2 activity by DEX in the intact cells. These results indicate that the production of LTC4 is predominantly regulated at a level of LTC4 synthase. The induction of new LTC4 synthase activity by RA and inhibition of the RA-induced activity by DEX are important regulatory mechanisms of LTC4 synthesis.
Department of Pediatrics, Saga Medical School, Japan.
Y
Y
Hamasaki
M
M
Abe
S
S
Matsumoto
T
T
Ichimaru
I
I
Kobayashi
E
E
Tanaka
M
M
Matsuo
N
N
Hara
S
S
Miyazaki
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism*; D017997:Leukotriene C4 / Q000096:biosynthesis*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016718:Arachidonic Acid; D017997:Leukotriene C4; D000001:Calcimycin; D014212:Tretinoin; D003907:Dexamethasone; D001094:Arachidonate 5-Lipoxygenase; D005982:Glutathione Transferase; D010741:Phospholipases A; D054467:Phospholipases A2