ArticleProceedings of the National Academy of Sciences of the United States of America2002
Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
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Who cites it
131 citing papers in PubMed, 369 citations in OpenAlex.
- The effect of the novel phosphodiesterase-4 inhibitor MEM 1414 on the allergen induced responses in mild asthma.BMC pulmonary medicine · 2014Trial
- Cannabinoid receptor-2 ligand beta-caryophyllene modulates inflammatory responses of bovine peripheral blood mononuclear cells in vitro.Scientific reports · 2026Article
- Identification of novel reproducible combinatorial genetic risk factors for myalgic encephalomyelitis in the DecodeME patient cohort and commonalities with long COVID.Journal of translational medicine · 2026Article
- PDE4B deficiency aids macrophage differentiation and contributes to Cryptococcus neoformans brain infection.PLoS pathogens · 2026Article
- The cAMP-phosphodiesterase PDE4B2 controls peroxisome proliferator-activated receptor γ expression and the initiation of adipogenesis in 3T3-L1 cells.American journal of physiology. Endocrinology and metabolism · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Article
- Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer's Disease.Cells · 2025Review
- Pharmacological characterization and preclinical evaluation of 11h: a novel, brain-penetrant PDE4 inhibitor for neurological disorders.Frontiers in pharmacology · 2025Article
- The role of compartmentalized β-AR/cAMP signaling in the regulation of lipolysis in white and brown adipocytes.The FEBS journal · 2025Review
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Potential of phosphodiesterase 4B inhibitors in the treatment of interstitial lung disease associated with autoimmune diseases.Clinical and experimental rheumatology · 2025Review
- Microglial circDlg1 modulates neuroinflammation by blocking PDE4B ubiquitination-dependent degradation associated with Alzheimer's disease.Theranostics · 2025Article
- Article
- Dysregulated Cyclic Nucleotide Metabolism in Alcohol-Associated Steatohepatitis: Implications for Novel Targeted Therapies.Biology · 2023Article
- Phosphodiesterase 4B inhibition: a potential novel strategy for treating pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Non-Selective PDE4 Inhibition Induces a Rapid and Transient Decrease of Serum Potassium in Mice.Biology · 2022Article
- The protective effect of Palmatine on depressive like behavior by modulating microglia polarization in LPS-induced mice.Neurochemical research · 2022Article
- 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
- Phosphodiesterase-4 Inhibitor Roflumilast-Mediated Protective Effect in Sepsis-Induced Late-Phase Event of Acute Kidney Injury: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2022Review
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Lipopolysaccharide (LPS) stimulation of the innate immune response requires the activation of signaling cascades that culminate in the synthesis and secretion of proinflammatory cytokines. Given the inhibitory effects of phosphodiesterase (PDE) inhibitors on LPS-induced cytokine production, we have investigated LPS responses in mice deficient in PDE4 (type 4 cAMP-specific PDE)-B and PDE4D. LPS stimulation of mouse peripheral leukocytes induced PDE4B mRNA accumulation and increased PDE4 activity. This response was completely absent in mice deficient in PDE4B but not PDE4D. LPS induction of tumor necrosis factor-alpha secretion by circulating leukocytes was decreased by approximately 90% in mice deficient in PDE4B but not in mice lacking PDE4D. The impaired LPS response was evident regardless of the LPS dose used for stimulation and was associated with a more than 90% decrease in tumor necrosis factor-alpha mRNA accumulation. A decreased responsiveness to LPS was also present in other inflammatory cells, including peritoneal and lung macrophages. These findings demonstrate that PDE4B gene activation by LPS constitutes a feedback regulation essential for an efficient immune response.
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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.