title: Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics.
abstract: BACKGROUND
  Reduced innate immunity responses as well as reduced T regulatory activities characterise bronchial asthma.
  
  
  OBJECTIVE
  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+/CD25 highly+ 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.
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell'Apparato Respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy. Electronic address: pace@ibim.cnr.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell'Apparato Respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Di Sano
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell'Apparato Respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell'Apparato Respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: Andreina
authors.initials: A
authors.lastname: Bruno
authors.affiliation: Department of Dermatology, University of Palermo, Palermo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Caputo
authors.affiliation: Dipartimento Biotecnologie e Neuroscienze Cliniche, Sezione di Otorinolaringoiatria, University of Palermo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gallina
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Unità di Immunopatologia e Farmacologia Clinica e Sperimentale dell'Apparato Respiratorio, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D019819:Budesonide / Q000494:pharmacology*; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D055815:Young Adult
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; C508609:IL10 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D019819:Budesonide
keywords: Corticosteroids; Immunoregulation; T lymphocytes; TLR