ArticleBritish journal of pharmacology2012
Roflumilast inhibits the release of chemokines and TNF-α from human lung macrophages stimulated with lipopolysaccharide.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 71 citations in OpenAlex.
- Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD.Respiratory research · 2019Trial
- The gut-lung axis: pathological crosstalk and inter-organ communication in chronic obstructive pulmonary disease and inflammatory bowel disease.Frontiers in immunology · 2026Review
- Roflumilast, a phosphodiesterase-4 (PDE4) inhibitor, induces respiratory frequency plasticity that is resistant to inflammation in neonatal rat in vitro preparations.Respiratory physiology & neurobiology · 2025Article
- Selective phosphodiesterase 4 inhibitor roflumilast reduces inflammation and lung injury in models of betacoronavirus infection in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Article
- Single-nucleotide polymorphism rs2910829 inOpen life sciences · 2024Article
- A European pharmacotherapeutic agent roflumilast exploring integrated preclinical and clinical evidence for SARS CoV-2 mediated inflammation to organ damage.British journal of clinical pharmacology · 2022Article
- Clinical Implication of Phosphodiesterase-4-Inhibition.International journal of molecular sciences · 2022Review
- Ruxolitinib inhibits cytokine production by human lung macrophages without impairing phagocytic ability.Frontiers in pharmacology · 2022Article
- The phosphodiesterase 4 inhibitor AA6216 suppresses activity of fibrosis-specific macrophages.Biochemistry and biophysics reports · 2021Article
- Inhaled Phosphodiesterase Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease.Drugs · 2021Review
- Identifying Lung Cancer Cell Markers with Machine Learning Methods and Single-Cell RNA-Seq Data.Life (Basel, Switzerland) · 2021Article
- Pyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors.RSC medicinal chemistry · 2021Article
- The PDE4 Inhibitor Tanimilast Blunts Proinflammatory Dendritic Cell Activation by SARS-CoV-2 ssRNAs.Frontiers in immunology · 2021Article
- Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages.Frontiers in pharmacology · 2021Article
- Roflumilast in Severely Ill Patients with Chronic Obstructive Pulmonary Disease with Frequent Exacerbations: Risk of Pneumonia Hospitalization and Severe Exacerbations.Journal of clinical medicine · 2020Article
- Metabolic reprograming of LPS-stimulated human lung macrophages involves tryptophan metabolism and the aspartate-arginosuccinate shunt.PloS one · 2020Article
- The Role of Toll-Like Receptors in the Production of Cytokines by Human Lung Macrophages.Journal of innate immunity · 2020Article
- Glucocorticoid Receptor α Mediates Roflumilast's Ability to Restore Dexamethasone Sensitivity in COPD.International journal of chronic obstructive pulmonary disease · 2020Article
- Clinical Relevance of the Anti-inflammatory Effects of Roflumilast on Human Bronchus: Potentiation by a Long-Acting Beta-2-Agonist.Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeLung macrophages are critically involved in respiratory diseases. This study assessed the effects of the PDE4 inhibitor roflumilast and its active metabolite, roflumilast N-oxide on the release of a range of chemokines (CCL2, 3, 4, CXCL1, 8, 10) and of TNF-α, from human lung macrophages, stimulated with bacterial lipopolysaccharide LPS. EXPERIMENTAL APPROACH: Lung macrophages isolated from resected human lungs were incubated with roflumilast, roflumilast N-oxide, PGE(2), the COX inhibitor indomethacin, the COX-2 inhibitor NS-398 or vehicle and stimulated with LPS (24 h). Chemokines, TNF-α, PGE(2) and 6-keto PGF(1α) were measured in culture supernatants by immunoassay. COX-2 mRNA expression was assessed with RT-qPCR. PDE activities were determined in macrophage homogenates. KEY
resultsExpression of PDE4 in lung macrophages was increased after incubation with LPS. Roflumilast and roflumilast N-oxide concentration-dependently reduced the LPS-stimulated release of CCL2, CCL3, CCL4, CXCL10 and TNF-α from human lung macrophages, whereas that of CXCL1 or CXCL8 was not altered. This reduction by the PDE4 inhibitors was further accentuated by exogenous PGE(2) (10 nM) but abolished in the presence of indomethacin or NS-398. Conversely, addition of PGE(2) (10 nM), in the presence of indomethacin restored inhibition by roflumilast. LPS also increased PGE(2) and 6-keto PGF(1α) release from lung macrophages which was associated with an up-regulation of COX-2 mRNA. CONCLUSIONS AND IMPLICATIONS: Roflumilast and roflumilast N-oxide reduced LPS-induced release of CCL2, 3, 4, CXCL10 and TNF-α in human lung macrophages.
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