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RESEARCH PRODUCT

Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma

subject

description

Background In asthma T cells are characterized by an increased activation state and by reduced apoptosis. Objective Because the clinical efficacy of inhaled corticosteroids combined with long-acting β 2 -agonists has been widely demonstrated in asthma, we studied, in vitro , the effect of fluticasone propionate (FP) and salmeterol alone and in combination on the activation and apoptosis of peripheral blood T cells (PBTs), on the expression of phosphorylated nuclear factor κB inhibitor (IκBα), and on the nuclear translocation of glucocorticoid receptor (GR) in PBTs from asthmatic subjects. Methods Apoptosis was evaluated on the basis of annexin V binding, whereas the expression of caspases 8 and 3 and phosphorylated IκBα, as well as the nuclear translocation of the GR, were evaluated by means of Western blot analysis. Results FP alone increases and salmeterol alone does not affect T-cell apoptosis. The combination of FP and salmeterol significantly increases PBT apoptosis in comparison with FP alone. FP at the lower concentration, when combined with salmeterol, is equivalent to FP at the higher concentration in inducing PBT apoptosis. The synergy in the induction of cell apoptosis is associated with more efficient activation of caspases 8 and 3. FP plus salmeterol is also able to synergistically reduce the expression of phosphorylated IκBα, thus limiting nuclear factor κB activation. The synergy was related to an increased nuclear translocation of the GR. Conclusion This study shows that the combination of FP and salmeterol is able to control PBT activation in asthmatic patients more efficiently than FP alone and with a lower concentration of steroids.