Fluoxetine action on murine T-lymphocyte proliferation: participation of PKC activation and calcium mobilisation.
The present study was undertaken to analyse the effect of fluoxetine upon murine T-lymphocyte proliferation. We found that fluoxetine exerted a dual effect, which depended on the degree of lymphocyte activation: at mitogenic concentration (2 microg/mL) of concavalin A (Con A), we observed an inhibitory effect on cellular proliferation, whereas, on submitogenic Con A concentration (1 microg/mL), fluoxetine stimulated the cellular response. Given these facts, we studied PKC activation and calcium mobilisation in both stimulatory and inhibitory effects of fluoxetine on T-cell proliferation. We observed that fluoxetine increased PKC translocation obtained with 1 microg/mL Con A concentration, whereas PKC was degraded when 2 microg/mL was used. This mechanism is thought to be mediated by calcium mobilisation. According to our results, fluoxetine seemed to modulate calcium influx, which, in turn, would influence PKC translocation, modulating the immune response.
Edgar
V A
VA
Centro De Estudios Farmacólogicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina (CONICET), Buenos Aires.
Genaro
A M
AM
Cremaschi
G
G
Sterin-Borda
L
L
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003208:Concanavalin A; D004789:Enzyme Activation; D005473:Fluoxetine / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D005473:Fluoxetine; D003208:Concanavalin A; D011493:Protein Kinase C; D002118:Calcium