GLUCOCORTICOIDS INHIBIT THE CYTOKINE-INDUCED PROLIFERATION OF MAST-CELLS, THE HIGH-AFFINITY IGE RECEPTOR-MEDIATED EXPRESSION OF TNF-ALPHA, AND THE IL-10-INDUCED EXPRESSION OF CHYMASES

Mast cells are a heterogeneous family of immune cells that, when activ ated through their high affinity IgE receptors (Fc epsilon RI), releas e various granule mediators (e.g., neutral proteases and serglycin pro teoglycans) and proinflammatory cytokines (e.g., IL-6 and TNF-alpha), We and others have shown that the growth and differentiation of immatu re, nontransformed mouse bone marrow-derived mast cells (mBMMC) can be regulated in vitro by IL-3, IL-10, and c-kit ligand. We now report th at glucocorticoids inhibit the c-kit ligand- and IL-3-induced prolifer ation of mBMMC, the Fc epsilon RI-mediated expression of TNF-alpha, an d the IL-10-mediated expression of the two chymases designated mouse m ast cell protease (mMCP)-1 and mMCP-2. In contrast, glucocorticoids in duce mBMMC to increase their expression of serglycin proteoglycan and carboxypeptidase A, As assessed by nuclear run-on and RNA blot analyse s, dexamethasone inhibited the IL-10-mediated expression of mMCP-1 and mMCP-2, primarily by inducing rapid degradation of their transcripts. The stimulative effect on serglycin proteoglycan expression and the i nhibitory effect on chymase expression were dose and time dependent an d glucocorticoid specific, These findings indicate that glucocorticoid s exert profound and diverse effects on the growth, cytokine expressio n, and granule differentiation of mouse mast cells, and that at least some of this regulation occurs through a post-transcriptional mechanis m.