Regulation of mouse mast cell surface FcεRI expression by dexamethasone

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Abstract
It is now clear that the mast cell's functional response to IgE-dependent stimulation can be influenced significantly by the level of expression of the high-affinity IgE receptor (FcεRI) on the cell's surface. Thus, modulation of FcεRI surface expression represents a potentially important 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 FcεRI expression either in the presence or absence of IgE, an up-regulator of the mast cell surface FcεRI level. In the absence of IgE, DEX decreased the surface FcεRI levels in mouse peritoneal mast cells, mouse bone marrow-derived cultured mast cells and a mouse mast cell line, Cl.MC/C57.1. Moreover, DEX also partially suppressed the ability of IgE to enhance surface expression of FcεRI in these cells. Three different glucocorticoids, DEX, methylprednisolone and hydrocortisone, suppressed FcεRI expression in mast cells, whereas sex steroids, i.e. estradiol, progesterone and testosterone, did not, indicating that the FcεRI-suppressing effect is glucocorticoid specific. On the other hand, DEX did not affect levels of FcεRI α, β or γ mRNA, suggesting that its ability to decrease surface FcεRI reflects a post-transcriptional mechanism. Finally, DEX-treated mast cells showed a reduced degranulation response to antigenic stimulation through down-regulation of surface FcεRI expression in addition to DEX-induced changes in downstream signals. These results show that mast cell surface FcεRI expression is suppressed by glucocorticoids in both the presence and absence of IgE, and suggest that reduction of mast cell surface FcεRI levels may be one of the favorable anti-allergic actions of glucocorticoids.