Background: Reduced innate immunity responses as well as reduced T regulatory activities characterise bronchial asthma. Objectives: In this study the effect of budesonide on the expression of TLR4 and TLR2 in T regulatory lymphocyte sub-population was assessed. Methods: TLR4 and TLR2 expression in total peripheral blood mononuclear cells (PBMC), in CD4+/CD25+ and in CD4+/CD25- was evaluated, by flow cytometric analysis, in mild intermittent asthmatics (n = 14) and in controls (n = 11). The in vitro effects of budesonide in modulating: TLR4 and TLR2 expression in controls and in asthmatics; IL-10 expression and cytokine release (IL-6 and TNF-α selected by a multiplex assay) in asthmatics were also explored. Results: TLR4 and TLR2 were reduced in total PBMC from asthmatics in comparison to PBMC from controls. CD4+CD25+ cells expressed at higher extent TLR2 and TLR4 in comparison to CD4+CD25- cells. Budesonide was able to increase the expression of TLR4, TLR2 and IL-10 in CD4+/CD25highly+ cells from asthmatics. TLR4 ligand, LPS induced Foxp3 expression. Budesonide was also able to reduce the release of IL-6 and TNF-α by PBMC of asthmatics. Conclusions: Budesonide potentiates the activity of Treg by increasing TLR4, TLR2 and IL-10 expression. This event is associated to the decreased release of IL-6 and TNF-α in PBMC treated with budesonide. These findings shed light on new mechanisms by which corticosteroids, drugs widely used for the clinical management of bronchial asthma, control T lymphocyte activation.

Pace, E., Di Sano, C., Ferraro, M., Bruno, A., Caputo, V., Gallina, S., et al. (2015). Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics. PULMONARY PHARMACOLOGY & THERAPEUTICS, 32, 93-100 [10.1016/j.pupt.2015.02.003].

Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics

DI SANO, Caterina;BRUNO, Andreina;CAPUTO, Valentina;GALLINA, Salvatore;
2015

Abstract

Background: Reduced innate immunity responses as well as reduced T regulatory activities characterise bronchial asthma. Objectives: In this study the effect of budesonide on the expression of TLR4 and TLR2 in T regulatory lymphocyte sub-population was assessed. Methods: TLR4 and TLR2 expression in total peripheral blood mononuclear cells (PBMC), in CD4+/CD25+ and in CD4+/CD25- was evaluated, by flow cytometric analysis, in mild intermittent asthmatics (n = 14) and in controls (n = 11). The in vitro effects of budesonide in modulating: TLR4 and TLR2 expression in controls and in asthmatics; IL-10 expression and cytokine release (IL-6 and TNF-α selected by a multiplex assay) in asthmatics were also explored. Results: TLR4 and TLR2 were reduced in total PBMC from asthmatics in comparison to PBMC from controls. CD4+CD25+ cells expressed at higher extent TLR2 and TLR4 in comparison to CD4+CD25- cells. Budesonide was able to increase the expression of TLR4, TLR2 and IL-10 in CD4+/CD25highly+ cells from asthmatics. TLR4 ligand, LPS induced Foxp3 expression. Budesonide was also able to reduce the release of IL-6 and TNF-α by PBMC of asthmatics. Conclusions: Budesonide potentiates the activity of Treg by increasing TLR4, TLR2 and IL-10 expression. This event is associated to the decreased release of IL-6 and TNF-α in PBMC treated with budesonide. These findings shed light on new mechanisms by which corticosteroids, drugs widely used for the clinical management of bronchial asthma, control T lymphocyte activation.
http://www.elsevier.com/inca/publications/store/6/2/2/9/3/6/index.htt
Pace, E., Di Sano, C., Ferraro, M., Bruno, A., Caputo, V., Gallina, S., et al. (2015). Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics. PULMONARY PHARMACOLOGY & THERAPEUTICS, 32, 93-100 [10.1016/j.pupt.2015.02.003].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/189514
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