Role of protein kinase C and cAMP in fluoxetine effects on human T-cell proliferation

In this work, we studied the effect of fluoxetine on human T-lymphocyte proliferation using optimal and suboptimal concanavalin A concentrations, In particular, we analyzed the influence of fluoxetine on the kinases that are involved in intracellular signalling after stimulation with mitogens. We found that fluoxetine promoted the Ca2+-mediated proteolysis of protein kinase C (PKC) and increased cyclic-AMP (cAMP) levels, thereby impairing lymphocyte proliferation, when optimal concanavalin A concentrations were used. In contrast, when suboptimal concanavalin A concentrations were used, fluoxetine only increased PKC translocation, without modifying cAMP levels, leading to T-cell proliferation. According to our results, fluoxetine has a dual effect on T-cell proliferation by modulating the PKC and protein kinase A pathways. This mechanism is thought to be mediated through Ca2+ mobilization. (C) 1999 Elsevier Science B.V. All rights reserved.