Abstract
We investigated regulatory mechanisms for leukotriene C4 generation by rat basophilic leukemia-1 (RBL-1) cells. When RBL-1 cells were preincubated with or without retinoic acid (RA) for 16 hours and stimulated with calcium ionophore A23187, the cells under the former condition produced larger amount of LTC4 than the latter cells. Such the enhanced LTC4 production was significantly inhibited by up to 93.5% in the presence of DEX.
In the cell free system, the lysates of RA-preincubated cells showed higher LTC4 synthase activity than the control cell lysates. In the presence of DEX, such the induction of LTC4 synthase activity was significantly inhibited by up to 66.8%. This discrepancy of inhibition between the intact and cell free systems was attributed to additional inhibition of phospholipase A2 activity by DEX (26.4%) .
These results indicate that the production of LTC4 is regulated at a level of LTC4 synthase. The regulation and the induction of new LTC4 synthase activity by RA and its inhibition by DEX may operate as an important regulatory mechanism for LTC4 synthesis in allergic and inflammatory disorders.
