calcimycin and 8-azidoadenosine-3--5--monophosphate

Cyclic AMP has long been proposed to be the intracellular second messenger that conveys the inhibitory signal for T-cell activation and clonal T-cell proliferation. The present study further explores the mechanism by which the cAMP pathway regulates human T-lymphocyte interleukin-2 (IL-2) production and T-cell blastogenesis. Activation of adenylate cyclase, inhibition of cAMP-dependent phosphodiesterase, or the direct addition of the cell-permeable cAMP analog, 8-N3-cAMP, increased occupancy of intracellular cAMP receptors, inhibited IL-2 production, and reduced T-cell proliferation. However, inhibition of cAMP-dependent protein phosphorylation by N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8), a cell-permeable inhibitor of cyclic nucleotide-dependent protein kinase, partially restored IL-2 production. Our data support the conclusion that the cAMP pathway conveys an inhibitory signal for IL-2 production and T-cell proliferation via an integral protein phosphorylation step.

Topics: 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; Adenylyl Cyclases; Adolescent; Adult; Aged; Azides; Calcimycin; Cell Line; Colforsin; Cyclic AMP; Dose-Response Relationship, Immunologic; Female; Humans; Immunosuppressive Agents; Interleukin-1; Interleukin-2; Lymphocyte Activation; Male; Middle Aged; Phosphorylation; T-Lymphocytes; Tetradecanoylphorbol Acetate