Dexamethasone induces a down regulation of rat mast cell protease II content in rat basophilic leukaemia cells

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Abstract
Corticosteroids are widely used to treat severe allergic and inflammatory disease in which mast cells have been implicated as playing an important role. It has been previously shown thatin vivo treatment with large bolus doses of corticosteroid can induce a down regulation of the number of IMMC in the rat. Previousin vitro studies of the RBL cell line have shown that culture in the presence of high doses of dexamethasone can induce an increase in cellular histamine content similar to that induced by other agents known to reduce the rate of cell division such as 5-hydroxyurea or sodium butyrate. In our studies the rat mucosal mast cell like cell line RBL-2H3 was cultured in the continuous presence of dexamethasone for periods of up to 4 weeks. Cell-associated histamine levels were found not to increase significantly at the doses of the corticosteroid we used. Of greater interest was the observation that levels of the mucosal mast cell specific protease RMCPII were dramatically reduced in these dexamethasone-treated cultures even at doses that might be considered to be physiologically relevant. This effect could be observed at 3 days after dexamethasone treatment and a continued reduction of RMCPII content was noted up to 4 weeks, at which time RMCPII levels were less than 5% of the control values in 10−7M dexamethasone treated cells. 5-Hydroxyurea did not reduce cellular RMCPII content even at a concentration which substantially reduced the rate of cell division and significantly increased cell associated histamine content. Treatment with a range of doses of sodium butyrate did not significantly reduce RMCPII content even at relatively high concentrations that reduced the rate of cell division. Since mast cell proteases have been implicated in a number of disease processes, including the degradation of type-IV collagen and the activation of other potentially tissue destructive pathways, these findings could have important implications for the mechanism of action of corticosteroids in the treatment of diseases in which mast cells play a role and may also provide an interesting model for the study of mast cell mediator content regulation.