ArticleBritish journal of pharmacology1999
Suppression of human inflammatory cell function by subtype-selective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B.
Article in British journal of pharmacology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Pharmacological mechanism of roflumilast in the treatment of asthma-COPD overlap.Drug design, development and therapy · 2018Pooled it
- Phase 2, randomized, double-blind, placebo-controlled, 4-week study to evaluate the safety and efficacy of OPA- 15406 (difamilast), a new topical selective phosphodiesterase type-4 inhibitor, in Japanese pediatric patients aged 2-14 years with atopic dermatitis.The Journal of dermatology · 2020Trial
- Review
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- Anti-Inflammatory Effects of miR-369-3p via PDE4B in Intestinal Inflammatory Response.International journal of molecular sciences · 2024Article
- Targeting cAMP signaling and phosphodiesterase 4 for liver disease treatment.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2024Article
- Challenges and Future Trends in Atopic Dermatitis.International journal of molecular sciences · 2023Review
- Clinical Implication of Phosphodiesterase-4-Inhibition.International journal of molecular sciences · 2022Review
- Regulation of PD-L1 expression is a novel facet of cyclic-AMP-mediated immunosuppression.Leukemia · 2021Article
- Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer.NPJ breast cancer · 2021Article
- Phosphodiesterase 4A confers resistance to PGE2-mediated suppression in CD25EMBO reports · 2021Article
- Roflumilast (Daliresp®) to reduce acute pulmonary events in fibrotic sarcoidosis: a multi-center, double blind, placebo controlled, randomized clinical trial.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2021Article
- Phosphodiesterase 4 inhibitors attenuate virus-induced activation of eosinophils from asthmatics without affecting virus binding.Pharmacology research & perspectives · 2020Article
- Comparative Assessment of the New PDE7 Inhibitor - GRMS-55 and Lisofylline in Animal Models of Immune-Related Disorders: A PK/PD Modeling Approach.Pharmaceutical research · 2020Article
- Efficacy and safety of topical OPA-15406, a new phosphodiesterase 4 inhibitor, in Japanese patients with atopic dermatitis for 8 weeks: A phase 2, randomized, double-blind, placebo-controlled study.The Journal of dermatology · 2019Article
- Identification of a Selective PDE4B Inhibitor FromFrontiers in pharmacology · 2019Article
- Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors.Arthritis research & therapy · 2015Article
- Phosphodiesterase inhibitors as therapeutics for traumatic brain injury.Current pharmaceutical design · 2015Review
- Effects of inactivated Bordetella pertussis on phosphodiesterase in the lung of ovalbumin sensitized and challenged rats.Pulmonary medicine · 2014Article
- Phosphodiesterase 4-targeted treatments for autoimmune diseases.BMC medicine · 2013Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Of the four major phosphodiesterase 4 (PDE4) subtypes, PDE4A, PDE4B and PDE4D are widely expressed in human inflammatory cells, including monocytes and T lymphocytes. We explored the functional role of these subtypes using ten subtype-selective PDE4 inhibitors, each belonging to one of two classes: (i) dual PDE4A/PDE4B inhibitors or (ii) PDE4D inhibitors. 2. These compounds were evaluated for their ability to inhibit antigen-stimulated T-cell proliferation and bacterial lipopolysaccharide (LPS)-stimulated tumour necrosis factor alpha (TNFalpha) release from peripheral blood monocytes. 3. All compounds inhibited T-cell proliferation in a concentration-dependent manner; with IC50 values distributed over an approximately 50 fold range. These compounds also inhibited TNFalpha release concentration-dependently, with a wider ( approximately 1000 fold) range of IC50 values. 4. In both sets of experiments, mean IC50 values were significantly correlated with compound potency against the catalytic activity of recombinant human PDE4A or PDE4B when analysed by either linear regression of log IC50 values or by Spearman's rank-order correlation. The correlation between inhibition of inflammatory cell function and inhibition of recombinant PDE4D catalytic activity was not significant in either analysis. 5. These results suggest that PDE4A and/or PDE4B may play the major role in regulating these two inflammatory cell functions but do not rule out PDE4D as an important mediator of other activities in mononuclear leukocytes and other immune and inflammatory cells. Much more work is needed to establish the functional roles of the PDE4 subtypes across a broader range of cellular functions and cell types.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.