ArticleNature communications2013
Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD.
Article in Nature communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 62 citations in OpenAlex.
- The protective effect of Schisandrin C against methicillin-resistantAntimicrobial agents and chemotherapy · 2026Article
- Establishing PDE4 as a Novel Target of Urolithin-A in Mitigating LPS-induced Inflammation in Retinal Pigmented Epithelium Cells.Pharmaceutical research · 2025Article
- Targeting Phosphodiesterase 4 in Gastrointestinal and Liver Diseases: From Isoform-Specific Mechanisms to Precision Therapeutics.Biomedicines · 2025Review
- Cross-Sensitization between Binge Eating and Binge Drinking in a Novel C57BL/6NJ Murine Model of Disease Comorbidity Requires PDE4B Activation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Preliminary exploration of mRNA, lncRNA, and miRNA expressions in the bovine jejunum unveils novel aspects of Mycobacterium avium subspecies paratuberculosis infections.BMC genomics · 2025Article
- Amlexanox Ameliorates Traumatic Brain Injury by Restoring Autophagy-Lysosomal Function via cAMP Signaling Modulation.International journal of biological sciences · 2025Article
- Zoledronic Acid Accelerates ER Stress-Mediated Inflammation by Increasing PDE4B Expression in Bisphosphonate-Related Osteonecrosis of the Jaw.Applied biochemistry and biotechnology · 2024Article
- Anti-inflammatory Effect of a Limonin Derivative In Vivo and Its Mechanisms in RAW264.7 Cells.Inflammation · 2023Article
- Potential use of EGFR-targeted molecular therapies for tumor suppressor CYLD-negative and poor prognosis oral squamous cell carcinoma with chemoresistance.Cancer cell international · 2022Article
- FGF1 and insulin control lipolysis by convergent pathways.Cell metabolism · 2022Article
- The regulatory role of PDE4B in the progression of inflammatory function study.Frontiers in pharmacology · 2022Review
- Effects of cigarette smoke on Haemophilus influenzae-induced otitis media in a rat model.Scientific reports · 2021Article
- Nitrosative Stress and Human Disease: Therapeutic Potential of Denitrosylation.International journal of molecular sciences · 2021Review
- The Extremophilic Actinobacteria: From Microbes to Medicine.Antibiotics (Basel, Switzerland) · 2021Review
- The Messenger Apps of the cell: Extracellular Vesicles as Regulatory Messengers of Microglial Function in the CNS.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Vinpocetine SuppressesJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Cilomilast Ameliorates Renal Tubulointerstitial Fibrosis by Inhibiting the TGF-β1-Smad2/3 Signaling Pathway.Frontiers in medicine · 2020Article
- Circular RNAs in human and vertebrate neural retinas.RNA biology · 2019Article
- Following spinal cord injury, PDE4B drives an acute, local inflammatory response and a chronic, systemic response exacerbated by gut dysbiosis and endotoxemia.Neurobiology of disease · 2019Article
- Increased intracellular ClMucosal immunology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
The deubiquitinase CYLD acts as a key negative regulator to tightly control overactive inflammation. Most anti-inflammatory strategies have focused on directly targeting the positive regulator, which often results in significant side effects such as suppression of the host defence response. Here, we show that inhibition of phosphodiesterase 4B (PDE4B) markedly enhances upregulation of CYLD expression in response to bacteria, thereby suggesting that PDE4B acts as a negative regulator for CYLD. Interestingly, in Cyld-deficient mice, inhibition of PDE4B no longer suppresses inflammation. Moreover, PDE4B negatively regulates CYLD via specific activation of JNK2 but not JNK1. Importantly, ototopical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal model, thus demonstrating the therapeutic potential of targeting PDE4. These studies provide insights into how inflammation is tightly regulated via the inhibition of its negative regulator and may also lead to the development of new anti-inflammatory therapeutics that upregulate CYLD expression.
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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.