PT  - JOURNAL ARTICLE
AU  - Jie Ji
AU  - Ida von Schéele
AU  - Bo Billing
AU  - Barbro Dahlén
AU  - Ann-Sofie Lantz
AU  - Kjell Larsson
AU  - Lena Palmberg
TI  - The effect of budesonide on TLR expression in alveolar macrophages from smokers
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P1477
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P1477.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P1477.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - IntroductionAlveolar macrophages (AM) from smokers with and without chronic obstructive pulmonary disease (COPD) express less toll-like receptor 2 (TLR2) than non-smokers. This reduced TLR2-expression may facilitate bacterial colonization and exacerbation in smokers with COPD. In primary bronchial epithelial cells, exposure of TLR-ligands/TNF with glucocorticosteroid increased TLR2 mRNA expression and reduced IL-8 release. The aim was to compare TLR expression and the effect of a glucocorticosteroid after stimulation with TLR-ligands on AM from smokers with and without COPD compared with healthy controls.MethodsBronchoalveolar lavage was performed and AMs were isolated from smokers with and without COPD and healthy controls (n=10 from each group) and stimulated ex vivo with peptidoglycan (PGN) or lipopolysaccharide (LPS) ±budesonide (Bud). Antibodies to TLR2 and TLR4 were added before LPS or PGN stimulation ±Bud. Inflammatory biomarkers were detected by ELISA, and TLR mRNA expression was analyzed by RT-PCR.ResultsStimulation with LPS and PGN increased IL-8 release in all groups. Bud attenuated LPS –induced IL-8 release in all groups, but PGN + Bud reduced IL-8 release only in healthy controls. The combination of Bud with LPS or PGN upregulated TLR2 expression in both smoker groups. Blocking TLR2 before stimulating the cells with PGN ±Bud reduced IL-8 release compared with the unblocked situation.Conclusion Stimulation with PGN and Bud reduced IL-8 release only in non-smokers. The combination of PGN and Bud upregulated TLR2 expression in smokers. Our findings that glucocorticosteroid therapy strengthens our immune defense pathways may have implication during exacerbation caused by microorganisms.