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cAMP‐elevating agents suppress dendritic cell function
Author(s) -
Kambayashi Taku,
Wallin Robert P. A.,
Ljunggren HansGustaf
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.6.903
Subject(s) - rolipram , antigen presentation , autoimmunity , phosphodiesterase , biology , immunology , major histocompatibility complex , dendritic cell , inflammation , tumor necrosis factor alpha , immune system , antigen processing , t cell , biochemistry , enzyme
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 α 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.