Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD
Jie Ji,1 Ida von Schéele,1 Bo Billing,2 Barbro Dahlén,2 Ann-Sofie Lantz,2 Kjell Larsson,1 Lena Palmberg1 1Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Department of Medicine, Karolinska Institutet, Karolinska Univers...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2016-05-01
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| Series: | International Journal of COPD |
| Subjects: | |
| Online Access: | https://www.dovepress.com/effects-of-budesonide-on-toll-like-receptor-expression-in-alveolar-mac-peer-reviewed-article-COPD |
| _version_ | 1818144244616921088 |
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| author | Ji J von Schéele I Billing B Dahlén B Lantz AS Larsson K Palmberg L |
| author_facet | Ji J von Schéele I Billing B Dahlén B Lantz AS Larsson K Palmberg L |
| author_sort | Ji J |
| collection | DOAJ |
| description | Jie Ji,1 Ida von Schéele,1 Bo Billing,2 Barbro Dahlén,2 Ann-Sofie Lantz,2 Kjell Larsson,1 Lena Palmberg1 1Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Introduction: Alveolar macrophages (AMs) are equipped with innate immune receptors such as toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4). In primary bronchial epithelial cells, exposure of toll-like receptor (TLR) ligands or tumor necrosis factor-alpha (TNF-α) increased TLR2 mRNA expression and reduced interleukin-8 (IL-8) release when coincubated with glucocorticosteroids. The aim of this study was to compare TLR2 and TLR4 expression levels and the effect of a glucocorticosteroid after stimulation with TLR ligands on AMs from smokers with and without COPD compared with the healthy controls. Subjects and methods: Bronchoalveolar lavage was performed, and AMs were isolated from smokers with (n=10) and without COPD (n=11) and healthy controls (n=10) and stimulated ex vivo with peptidoglycan (PGN), lipopolysaccharide (LPS), or TNF-α ± budesonide (Bud). Blocking antibodies to TLR2 or TLR4 were added before stimulation with LPS or PGN ± Bud, respectively. The release of proinflammatory cytokine (TNF-α), chemoattractant (CXCL8), and TLR expression was analyzed by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Results: LPS, PGN, and TNF-α induced an increased release of IL-8 and TNF-α in the AMs in all the groups independent of smoking or disease. These responses were inhibited by a glucocorticosteroid (Bud) in all the three groups, except PGN-induced IL-8 secretion in smokers without COPD. Bud increased TLR2 expression in the healthy controls and smokers without COPD. Costimulation of TLR ligands and Bud significantly enhanced TLR2 mRNA expression in both groups of smokers compared with TLR ligands alone. In smokers, costimulation with PGN and Bud significantly increased TLR2 expression when compared with Bud alone. On stimulation with the TLR4 agonist, LPS downregulated TLR4 mRNA expression in all the three groups. Conclusion: The combination of glucocorticosteroids with TLR ligands can increase TLR2 expression, thereby improving host defense in smokers. Also this combination can decrease the secretion of proinflammatory cytokines and chemokines as an anti-inflammatory response. Our findings indicate that glucocorticosteroid therapy strengthens immune defense pathways, which may have implication during exacerbation caused by microorganisms. Keywords: smokers, lipopolysaccarid, peptidoglycan, glucocorticosteroid |
| first_indexed | 2024-12-11T11:44:29Z |
| format | Article |
| id | doaj.art-f20fce70b8414ff89ffbcc535664a518 |
| institution | Directory Open Access Journal |
| issn | 1178-2005 |
| language | English |
| last_indexed | 2024-12-11T11:44:29Z |
| publishDate | 2016-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of COPD |
| spelling | doaj.art-f20fce70b8414ff89ffbcc535664a5182022-12-22T01:08:31ZengDove Medical PressInternational Journal of COPD1178-20052016-05-012016Issue 11035104326951Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPDJi Jvon Schéele IBilling BDahlén BLantz ASLarsson KPalmberg LJie Ji,1 Ida von Schéele,1 Bo Billing,2 Barbro Dahlén,2 Ann-Sofie Lantz,2 Kjell Larsson,1 Lena Palmberg1 1Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Introduction: Alveolar macrophages (AMs) are equipped with innate immune receptors such as toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4). In primary bronchial epithelial cells, exposure of toll-like receptor (TLR) ligands or tumor necrosis factor-alpha (TNF-α) increased TLR2 mRNA expression and reduced interleukin-8 (IL-8) release when coincubated with glucocorticosteroids. The aim of this study was to compare TLR2 and TLR4 expression levels and the effect of a glucocorticosteroid after stimulation with TLR ligands on AMs from smokers with and without COPD compared with the healthy controls. Subjects and methods: Bronchoalveolar lavage was performed, and AMs were isolated from smokers with (n=10) and without COPD (n=11) and healthy controls (n=10) and stimulated ex vivo with peptidoglycan (PGN), lipopolysaccharide (LPS), or TNF-α ± budesonide (Bud). Blocking antibodies to TLR2 or TLR4 were added before stimulation with LPS or PGN ± Bud, respectively. The release of proinflammatory cytokine (TNF-α), chemoattractant (CXCL8), and TLR expression was analyzed by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Results: LPS, PGN, and TNF-α induced an increased release of IL-8 and TNF-α in the AMs in all the groups independent of smoking or disease. These responses were inhibited by a glucocorticosteroid (Bud) in all the three groups, except PGN-induced IL-8 secretion in smokers without COPD. Bud increased TLR2 expression in the healthy controls and smokers without COPD. Costimulation of TLR ligands and Bud significantly enhanced TLR2 mRNA expression in both groups of smokers compared with TLR ligands alone. In smokers, costimulation with PGN and Bud significantly increased TLR2 expression when compared with Bud alone. On stimulation with the TLR4 agonist, LPS downregulated TLR4 mRNA expression in all the three groups. Conclusion: The combination of glucocorticosteroids with TLR ligands can increase TLR2 expression, thereby improving host defense in smokers. Also this combination can decrease the secretion of proinflammatory cytokines and chemokines as an anti-inflammatory response. Our findings indicate that glucocorticosteroid therapy strengthens immune defense pathways, which may have implication during exacerbation caused by microorganisms. Keywords: smokers, lipopolysaccarid, peptidoglycan, glucocorticosteroidhttps://www.dovepress.com/effects-of-budesonide-on-toll-like-receptor-expression-in-alveolar-mac-peer-reviewed-article-COPDCOPDalveolar macrophagestoll-like receptorglucocorticsteroid |
| spellingShingle | Ji J von Schéele I Billing B Dahlén B Lantz AS Larsson K Palmberg L Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD International Journal of COPD COPD alveolar macrophages toll-like receptor glucocorticsteroid |
| title | Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD |
| title_full | Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD |
| title_fullStr | Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD |
| title_full_unstemmed | Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD |
| title_short | Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD |
| title_sort | effects of budesonide on toll like receptor expression in alveolar macrophages from smokers with and without copd |
| topic | COPD alveolar macrophages toll-like receptor glucocorticsteroid |
| url | https://www.dovepress.com/effects-of-budesonide-on-toll-like-receptor-expression-in-alveolar-mac-peer-reviewed-article-COPD |
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