ArticleJournal of clinical medicine2019
LABAs and p38MAPK Inhibitors Reverse the Corticosteroid-Insensitivity of IL-8 in Airway Smooth Muscle Cells of COPD.
Article in Journal of clinical medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- p38 MAPK signaling in chronic obstructive pulmonary disease pathogenesis and inhibitor therapeutics.Cell communication and signaling : CCS · 2023Pooled it
- Causal Relationship Between Methotrexate and Chronic Obstructive Pulmonary Disease: A Study Based on Network Toxicology and Mendelian Randomization.International journal of chronic obstructive pulmonary disease · 2026Article
- Molecular Study from the Signaling Pathways of Four PotentialInternational journal of molecular sciences · 2025Article
- Network Pharmacology and Experimental Validation of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-155-5p.Combinatorial chemistry & high throughput screening · 2025Article
- The cGAS-STING pathway in COPD: targeting its role and therapeutic potential.Respiratory research · 2024Review
- Pathological Mechanism and Targeted Drugs of COPD.International journal of chronic obstructive pulmonary disease · 2022Review
- Potential cellular endocrinology mechanisms underlying the effects of Chinese herbal medicine therapy on asthma.Frontiers in endocrinology · 2022Review
- Dexamethasone and p38 MAPK inhibition of cytokine production from human lung fibroblasts.Fundamental & clinical pharmacology · 2021Article
- Therapeutic Effects and Molecular Mechanisms of Bioactive Compounds Against Respiratory Diseases: Traditional Chinese Medicine Theory and High-Frequency Use.Frontiers in pharmacology · 2021Review
- Resveratrol extracted from Chinese herbal medicines: A novel therapeutic strategy for lung diseases.Chinese herbal medicines · 2020Review
- Determining Pharmacological Mechanisms of Chinese Incompatible Herbs Fuzi and Banxia in Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study.Evidence-based complementary and alternative medicine : eCAM · 2020Article
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
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Abstract
Airway inflammation in chronic obstructive pulmonary disease (COPD) is partially insensitive/resistant to inhaled corticosteroids (ICS). ICS plus bronchodilator therapy has been discussed for COPD phenotypes with frequent exacerbations and participation of corticosteroid-sensitive type 2/eosinophilic inflammation. Neutralization of non-type 2/IL-8-associated airway inflammation by reversion of its corticosteroid-resistance might be a future strategy for other phenotypes. Human airway smooth muscle cells (HASMCs) produce corticosteroid-insensitive IL-8 in response to TNFα or LPS in stable disease stages or bacteria-induced exacerbations, respectively. p38-mitogen-activated-protein-kinases (p38MAPKs) are alternative therapeutic targets. Hypothesis: long-acting-β2-agonists (LABAs) reverse the corticosteroid-insensitivity of IL-8 by p38MAPK inhibition in HASMCs. Cultivated HASMCs from COPD subjects were pre-incubated with formoterol, salmeterol, fluticasone-propionate, BIRB796 (p38MAPKα, -γ, -δ inhibitor), and/or SB203580 (p38MAPKα and -β inhibitor) before stimulation with TNFα or LPS. IL-8 and MAPK-activities were measured by ELISA. Formoterol, salmeterol, and fluticasone did not or hardly reduced TNFα- or LPS-induced IL-8. BIRB796 and SB203580 reduced TNFα-induced IL-8. SB203580 reduced LPS-induced IL-8. Fluticasone/formoterol, fluticasone/salmeterol, and fluticasone/BIRB796, but not fluticasone/SB203580 combinations, reduced TNFα-induced IL-8 stronger than single treatments. All combinations including fluticasone/SB203580 reduced LPS-induced IL-8 stronger than single treatments. TNFα induced p38MAPKα and -γ activity. LPS induced p38MAPKα activity. Formoterol reduced TNFα-induced p38MAPKγ and LPS-induced p38MAPKα activity. LABAs reverse the corticosteroid-insensitivity of IL-8 in airway smooth muscles via p38MAPKγ in stable disease and via p38MAPKα in exacerbations. Our pre-clinical data indicate a utility for also adding ICS in non-type 2 inflammatory COPD phenotypes to bronchodilator therapy. Depending on phenotype and disease stage, isoform-specific p38MAPK blockers might also reverse corticosteroid-resistance in COPD.
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