Dexamethasone increases intracellular cyclic AMP concentration in murine Tlymphocyte cell lines

The effects of the synthetic glucocorticoid dexamethasone on the cAMP conte nt of murine T lymphocyte cell lines has been investigated. Incubation of t he 3B4.15 T cell hybrids with dexamethasone results in an average 5-fold in crease in intracellular cyclic AMP levels after 6 h of treatment. This phen omenon is abolished in the presence of RU486 and of cycloheximide, indicati ng that it requires binding of the drug to the intracellular glucocorticoid s receptor and de novo protein synthesis. Dexamethasone-induced elevation o f intracellular cyclic AMP correlates with both an increase in adenylate cy clase activity and a decrease in phosphodiesterase activity in T cell hybri ds. This modulation of cyclic AMP metabolism is independent of serum-derive d factors, suggesting that it is not secondary to transmembrane receptor st imulation by an extracellular ligand. We propose that glucocorticoids inter fere with the homeostatic control of intracellular cAMP concentration, lead ing to a sustained increase in the content of this important second messeng er in murine T lymphocyte cell Lines. This study suggests that elevation of cAMP levels may represent one way by which glucocorticoids modulate the im mune response. (C) 2001 Elsevier Science Inc. All rights reserved.