Effect of prostaglandin E 2 and other intracellular cyclic AMP elevating agents on the mitogen induced mouse splenocyte proliferation in a serum free culture condition

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Prostaglandins (PGs) play an important role in the regulation of the host's immune responses to infection and inflammation. However, the mechanisms through which the PGs regulate immune functions are not well known. In the present study, we investigated the T cell specific mitogen Concanavalin A (Con A) induced mouse splenocyte proliferation in a serum free condition in vitro in the presence or absence of different doses of PGE 2, indomethacin, cholera toxin and forskolin. The Con A induced splenocyte proliferative responses were significantly inhibited following the addition of PGE 2 and were markedly enhanced in the presence of indomethacin (PG synthase inhibitor). As with PGE 2, both cholera toxin and forskolin, which increase intracellular cyclic AMP by activating stimulatory GTP binding protein (Gs protein) and adenylate cyclase respectively, inhibited splenocyte proliferation in a dose dependent manner. These data indicate that PGE 2 down regulated mitogen induced splenocyte proliferation and that blocking the production of endogenous PGs potentiated T-cell mitogen response. Further, these findings suggest that PGE 2 regulation of splenocyte proliferation is due to increasing intracellular cAMP through G protein transmembrane regulation of adenylate cyclase. This study also provided a defined experimental model to investigate mechanisms of the regulation of cellular function through the exogenous and endogenous mediators such as PGs and their intracellular signal transductions.