Glucocorticoids Suppress Calcium Mobilization and Phospholipid Hydrolysis in Anti-Ig Antibody-Stimulated B Cells
Abstract
Glucocorticoids have been shown to play a major role in influencing the activation of B lymphocytes. In view of our recent observation that dexamethasone exerts a marked suppressive effect on an early event in B cell activation that is stimulated by anti-Ig antibody, we investigated its activity on other stimuli that induce intracellular events similar to those produced by anti-Ig antibody. Because the intracellular events that occur after B cell stimulation with phorbol myristate acetate and the calcium ionosphere A23187 appear to mimic those that occur after B cell simultion with anti-Ig antibody, we studied whether the cellular responses elicited by these activation stimuli are affected in a similar fashion by dexamethasone. Our finding that anti-Ig- induced crosslinking of B cell surface Ig, as measured by surface capping was not inhibited by dexamethasone suggested that corticosteroids inhibit anti-Ig- induced B cell proliferation at a step distal to membrane Ig cross-linking and proximal to phosphatidylinositol bisphosphate hydrolysis. This hypothesis is supported by experiments presented in this manuscript which demonstrate that dexamethasone inhibits anti-Ig-stimulated phosphatidylinositol bisphosphate hydrolysis. Our data suggest that the immunomodulatory activity of glucocorticoids is exerted by binding to its nuclear receptor, thereby preventing the generation of second messengers required for cell activation after agonist-receptor interaction. Keywords: Reprints; Molecule molecule interactions; Calcium channels; Binding sites.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 15, 1987
- Accession Number
- ADA198620
Entities
People
- Carl H. June
- Gregory Dennis
- Junichi Ohara
- Junichiro Mizuguchi
- Kim Weatherspoon
Organizations
- Naval Medical Research Center