Dexamethasone increases intracellular cyclic AMP concentration in murine T lymphocyte cell lines.
The effects of the synthetic glucocorticoid dexamethasone on the cAMP content of murine T lymphocyte cell lines has been investigated. Incubation of the 3B4.15 T cell hybrids with dexamethasone results in an average 5-fold increase in intracellular cyclic AMP levels after 6 h of treatment. This phenomenon is abolished in the presence of RU486 and of cycloheximide, indicating that it requires binding of the drug to the intracellular glucocorticoids receptor and de novo protein synthesis. Dexamethasone-induced elevation of intracellular cyclic AMP correlates with both an increase in adenylate cyclase activity and a decrease in phosphodiesterase activity in T cell hybrids. This modulation of cyclic AMP metabolism is independent of serum-derived factors, suggesting that it is not secondary to transmembrane receptor stimulation by an extracellular ligand. We propose that glucocorticoids interfere with the homeostatic control of intracellular cAMP concentration, leading to a sustained increase in the content of this important second messenger in murine T lymphocyte cell lines. This study suggests that elevation of cAMP levels may represent one way by which glucocorticoids modulate the immune response.
Baus
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E
Animal Physiology Laboratory, Free University of Brussels, Avenue des Prof. Jeener et Brachet 12, 6041, Gosselies, Belgium.
Van Laethem
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F
Andris
F
F
Rolin
S
S
Urbain
J
J
Leo
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O
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D005938:Glucocorticoids / Q000494:pharmacology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006822:Hybrid Cells; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D005938:Glucocorticoids; D010726:Phosphodiesterase Inhibitors; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D003513:Cycloheximide; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine