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RESEARCH PRODUCT
Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics
Salvatore GallinaValentina CaputoMark GjomarkajAndreina BrunoElisabetta PaceCaterina Di SanoMaria Ferrarosubject
AdultMalePulmonary and Respiratory MedicineBudesonidemedicine.medical_treatmentLymphocyteIn Vitro TechniquesCorticosteroids; Immunoregulation; T lymphocytes; TLR; Adult; Asthma; Budesonide; Cytokines; Female; Flow Cytometry; Glucocorticoids; Humans; In Vitro Techniques; Interleukin-10; Leukocytes Mononuclear; Male; T-Lymphocytes Regulatory; Toll-Like Receptor 2; Toll-Like Receptor 4; Young Adult; Pulmonary and Respiratory Medicine; Pharmacology (medical); Biochemistry (medical); Medicine (all)T-Lymphocytes RegulatoryPeripheral blood mononuclear cellYoung AdultGlucocorticoidTLRT lymphocytemedicineCorticosteroidHumansPharmacology (medical)IL-2 receptorBudesonideCytokineGlucocorticoidsIn Vitro Techniquebusiness.industryMedicine (all)Biochemistry (medical)ImmunoregulationFlow CytometryAsthmaToll-Like Receptor 2Interleukin-10Toll-Like Receptor 4Interleukin 10TLR2Cytokinemedicine.anatomical_structureImmunologyLeukocytes MononuclearTLR4CytokinesFemalebusinessHumanmedicine.drugdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-06-01 | Pulmonary Pharmacology & Therapeutics |