Inhibition by dexamethasone of retinoic acid-induced enhancement of leukotriene C4 synthesis in rat basophilic leukemia-1 cells.

Abstract

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.

Interleukin-3 Regulates Development of the 5-Lipoxygenase/Leukotriene C4 Synthase Pathway in Mouse Mast Cells

“…LTC 4 synthase, also an integral nuclear envelope protein sharing 31% amino acid identity with FLAP (25), conjugates LTA 4 to reduced glutathione to form LTC 4 . Although LTC 4 synthase is induced in U937 cells during differentiation into monocyte/macrophage-like cells in response to treatment with dimethyl sulfoxide (26) and in RBL-1 cells treated with retinoic acid (27) as assessed by an increase in enzyme activity, no information exists on the transcriptional or translational regulation of this terminal enzyme. The expression of LTC 4 syn- …”

Leukotriene Synthesis Is Increased by Transcriptional Up-Regulation of 5-Lipoxygenase, Leukotriene A4Hydrolase, and Leukotriene C4Synthase in Asthmatic Children

“…Four LT-synthesizing enzymes, cytosolic phospholipase A 2 (cPLA 2 ), 5-LO, LTA 4 hydrolase, and LTC 4 synthase (LTC 4 syn), and an essential protein, five-lipoxygenase activating protein (FLAP), are consecutively involved in the synthesis of LTB 4 and LTC 4 in this metabolic pathway. Recent in vitro studies have demonstrated that these enzymes and their protein molecules are transcriptionally and/or post-transcriptionally up-regulated by various bioactive substances including interleukins (ILs) (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). These findings suggest that these enzyme activities are controlled by similar molecular mechanisms in vivo and are possibly up-regulated in bronchial asthma in which ILs and other bioactive substances are activated.…”

Inhibition of Leukotriene Synthesis by Honokiol in Rat Basophilic Leukemia Cells

“…RBL-1 cells produce LTC4 and LTB4 in amounts sufficiently large to be measured by high-performance liquid chromatography (HPLC) after induction of LTC4 synthase activity by treating with all /raw.s-retinoic acid (RA) at 0.1 ug/ml for 16 h and sub sequent stimulation with A23187 [13][14][15].…”