ArticleRespiratory research2015
Roflumilast improves corticosteroid resistance COPD bronchial epithelial cells stimulated with toll like receptor 3 agonist.
Article in Respiratory research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Roflumilast reduces the number of lung adenocarcinomas, inflammation, and emphysema in a smoking-induced mouse model.BMC pulmonary medicine · 2025Article
- Differential response to roflumilast in patients with chronic obstructive pulmonary disease: real-world evidence.Journal of thoracic disease · 2024Article
- How inhaled corticosteroids target inflammation in COPD.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- HAO1-mediated oxalate metabolism promotes lung pre-metastatic niche formation by inducing neutrophil extracellular traps.Oncogene · 2022Article
- Changes in Pulmonary Microenvironment Aids Lung Metastasis of Breast Cancer.Frontiers in oncology · 2022Review
- Article
- Using Blood Eosinophil Count as a Biomarker to Guide Corticosteroid Treatment for Chronic Obstructive Pulmonary Disease.Diagnostics (Basel, Switzerland) · 2021Review
- New putative insights into neprilysin (NEP)-dependent pharmacotherapeutic role of roflumilast in treating COVID-19.European journal of pharmacology · 2020Review
- CFTR targeted therapies: recent advances in cystic fibrosis and possibilities in other diseases of the airways.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- Glucocorticoid Receptor α Mediates Roflumilast's Ability to Restore Dexamethasone Sensitivity in COPD.International journal of chronic obstructive pulmonary disease · 2020Article
- Dexamethasone Inhibits Synergistic Induction of PDE4B Expression by Roflumilast and Bacterium NTHi.International journal of molecular sciences · 2018Article
- Steroid resistance and concomitant respiratory infections: A challenging battle in pulmonary clinic.EXCLI journal · 2017Article
- Extracellular ATP is involved in dsRNA-induced MUC5AC production via P2Y2R in human airway epithelium.Respiratory research · 2016Article
- Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells.Respiratory research · 2016Article
- Roflumilast: A Review in COPD.Drugs · 2015Review
- Differential anti-inflammatory effects of budesonide and a p38 MAPK inhibitor AZD7624 on COPD pulmonary cells.International journal of chronic obstructive pulmonary diseaseArticle
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChronic obstructive pulmonary disease (COPD) is characterised by chronic pulmonary inflammation punctuated by periods of viral exacerbations. Recent evidence suggests that the combination of roflumilast with corticosteroids may improve the compromised anti-inflammatory properties of corticosteroids in COPD. We analyzed differential and combination anti-inflammatory effects of dexamethasone and roflumilast N-oxide in human bronchial epithelial cells (HBECs) stimulated with viral toll like receptor (TLR) agonists.
methodsLung tissue and HBECs were isolated from healthy (n = 15), smokers (n = 12) and smokers with COPD (15). TLR3 expression was measured in lung tissue and in HBECs. IL-8 secretion was measured in cell cultures after TLR3 stimulation with poly I:C 10 μg/mL.
resultsWe found that TLR3 expression was increased by 1.95 fold (protein) and 2.5 fold (mRNA) in lung tissues from smokers with COPD and inversely correlated with lung function. The TLR3 agonist poly I:C 10 μg/mL increased the IL-8 release in HBECs that was poorly inhibited by dexamethasone in smokers (24.5%) and smokers with COPD (21.6%). In contrast, roflumilast showed similar inhibitory effects on IL-8 release in healthy (58.8%), smokers (56.6%) and smokers with COPD (50.5%). The combination of roflumilast N-oxide and dexamethasone showed additive inhibitory effects. Mechanistically, roflumilast N-oxide when combined with dexamethasone increased the expression of MKP1, and enhanced the inhibitory effects on phospho-p38, AP1 and NFκB activities which may explain the additive anti-inflammatory effects.
conclusionsAltogether, our data provide in vitro evidence for a possible clinical utility to add roflumilast on top of inhaled corticosteroid in COPD.
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