Am. J. Respir. Cell Mol. Biol., Vol 11, No. 1, Jul 1994, 49-56.
Inhibition by dexamethasone of retinoic acid-induced enhancement of leukotriene C4 synthesis in rat basophilic leukemia-1 cells
Y Hamasaki, M Abe, S Matsumoto, T Ichimaru, I Kobayashi, E Tanaka, M Matsuo, N Hara and S Miyazaki
Department of Pediatrics, Saga Medical School, Japan.
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.
