RESUMO
The effect of fluoxetine on mitogen-induced B-cell proliferation was studied. In particular, we analyzed the influence of fluoxetine on the signal transduction pathways triggered after stimulation with lipopolysaccharide (LPS) and anti-immunoglobulin M antibodies (anti-IgM). We showed that fluoxetine had a dual effect on anti-IgM-stimulated B-cell proliferation: at optimal anti-IgM concentration, fluoxetine inhibited proliferation, whereas at suboptimal anti-IgM concentration, the drug enhanced proliferation. Fluoxetine exerted only an inhibitory effect on LPS-induced B-cell proliferation. Calcium influx seemed to be involved in these effects.
Assuntos
Anticorpos Anti-Idiotípicos/farmacologia , Linfócitos B/efeitos dos fármacos , Fluoxetina/farmacologia , Lipopolissacarídeos/farmacologia , Animais , Antidepressivos de Segunda Geração/farmacologia , Linfócitos B/citologia , Transporte Biológico , Cálcio/metabolismo , Divisão Celular/efeitos dos fármacos , Interações Medicamentosas , Feminino , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB CRESUMO
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.
Assuntos
Antidepressivos de Segunda Geração/farmacologia , AMP Cíclico/fisiologia , Fluoxetina/farmacologia , Proteína Quinase C/fisiologia , Linfócitos T/efeitos dos fármacos , Adulto , Calcimicina/farmacologia , Cálcio/metabolismo , Divisão Celular/efeitos dos fármacos , Concanavalina A/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Feminino , Humanos , Ionóforos/farmacologia , Linfócitos T/citologia , Linfócitos T/enzimologiaRESUMO
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.
