Regulation of mouse mast cell surface Fc epsilon RI expression by dexamethasone

It is now clear that the mast cell's functional response to IgE-dependent s timulation can be Influenced significantly by the level of expression of th e high-affinity IgE receptor (Fc epsilon RI) on the cell's surface. Thus, m odulation of Fc epsilon RI surface expression represents a potentially impo rtant mechanism for regulating mast cell activity in allergic reactions. In this study, we examined whether a glucocorticoid, dexamethasone (DEX), can influence levels of mast cell Fc epsilon RI expression either in the prese nce or absence of IgE, an up-regulator of the mast cell surface Fc epsilon RI level. In the absence of IgE, DEX decreased the surface Fc epsilon RI le vels in mouse peritoneal mast cells, mouse bone marrow-derived cultured mas t cells and a mouse mast cell line, CI.MC/C57.1. Moreover, DEX also partial ly suppressed the ability of IgE to enhance surface expression of FceRI in these cells. Three different glucocorticoids, DEX, methylprednisolone and h ydrocortisone, suppressed FceRI expression in mast cells, whereas sex stero ids, i.e. estradiol, progesterone and testosterone, did not, indicating tha t the Fc epsilon RI-suppressing effect is glucocorticoid specific. On the o ther hand, DEX did not affect levels of Fc epsilon RI alpha, beta or gamma mRNA, suggesting that its ability to decrease surface Fc epsilon RI reflect s a post-transcriptional mechanism. Finally, DEX-treated mast cells showed a reduced degranulation response to antigenic stimulation through down-regu lation of surface Fc epsilon RI expression in addition to DEX-induced chang es in downstream signals. These results show that mast cell surface Fc epsi lon RI expression is suppressed by glucocorticoids in both the presence and absence of IgE, and suggest that reduction of mast cell surface Fc epsilon RI levels may be one of the favorable anti-allergic actions of glucocortic oids.