Inhibition of basophil histamine release by anti-inflammatory steroids. II. Studies on the mechanism of action.
The glucocorticosteroids inhibit the IgE-dependent release of histamine by human basophils with an order of potency that very closely parallels that found in vivo (i.e., triamcinolone acetonide greater than dexamethasone greater than beta-methasone greater than prednisolone greater than hydrocortisone much greater than progesterone approximately tetrahydrocortisone approximately 0). The effect is seen after a 24-hr preincubation with nanomolar to micromolar concentrations of glucocorticoid. In contrast, release of histamine stimulated by the formyl methionine containing peptide f-met-leu-phe, the calcium ionophore A23187, and the tumor-promoting phorbol diester 12-O-tetradecanoylphorbol-13-acetate was not inhibited by 24-hr incubation with the potent glucocorticoid dexamethasone. Dexamethasone inhibited anti-IgE-induced histamine release without altering its rate, suggesting that the glucocorticoids do not inhibit histamine release by elevating the intracellular level of cAMP. Dexamethasone did not consistently alter either the total or occupied basophil IgE Fc receptor number, and therefore the glucocorticoid effect does not appear to be due to the modulation of cell surface Fc epsilon receptor content. These data indicate that steroid hormones inhibit basophil IgE-dependent activation through a specific glucocorticoid receptor. The mechanism by which they do so appears not to involve an elevation of cAMP or a shedding of cell surface Fc epsilon receptors. Further, because the glucocorticoids did not inhibit release initiated by the PLA2-dependent stimuli f-met-leu-phe, A23187 and TPA, the inactivation of IgE-dependent histamine release by glucocorticoids may not be the result of PLA2 inhibition.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D006636:Histamine Release / Q000187:drug effects*; D007073:Immunoglobulin E / Q000276:immunology; D011961:Receptors, Fc / Q000502:physiology; D013256:Steroids / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D011961:Receptors, Fc; D013256:Steroids; D007073:Immunoglobulin E