cAMP-elevating agents suppress dendritic cell function.
The administration of cAMP-elevating agents affects a number of autoimmune and inflammatory conditions. Because dendritic cells (DCs) play a pivotal role in autoimmunity and inflammation, the isolated effects of cAMP-elevating agents on the function of DCs was examined. In a dose-dependent manner, 8-Bromo cAMP, prostaglandin E(2), and 3-isobutyl-1-methylxanthine inhibited tumor necrosis factor alpha release and suppressed antigen presentation by DCs. The same effect was observed with rolipram, a specific inhibitor of phosphodiesterase type 4, but not with inhibitors of other phosphodiesterases. The decreased antigen presentation by DCs was associated with an enhanced production of interleukin (IL)-10 and with lower major histocompatibility complex type II (MHC II) expression. Furthermore, the inhibition of antigen presentation and MHC II expression was significantly reversed by treatment of DCs with neutralizing antibody against IL-10, suggesting the involvement of an IL-10-dependent mechanism. Taken together, these results might explain why certain cAMP-elevating agents such as rolipram are effective in blocking autoimmunity and inflammation.
Kambayashi
T
T
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Wallin
R P
RP
Ljunggren
H G
HG
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D020889:Rolipram; D015056:1-Methyl-3-isobutylxanthine