ArticleThe Journal of biological chemistry2012
Phosphodiesterase 4B mediates extracellular signal-regulated kinase-dependent up-regulation of mucin MUC5AC protein by Streptococcus pneumoniae by inhibiting cAMP-protein kinase A-dependent MKP-1 phosphatase pathway.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Role of the cAMP-PKA-NF-κB pathway in Mucin1 over-expression in A549 cells during Respiratory syncytial virus infection.BMC infectious diseases · 2023Article
- Associations of Serum Clara Cell Protein 16 with Severity and Prognosis in Adults with Community-Acquired Pneumonia.International journal of general medicine · 2023Article
- Negative Cross-Talk between TLR2/4-Independent AMPKα1 and TLR2/4-Dependent JNK RegulatesJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Loss of NLRP3 increases bacterial cystitis via IRAKM.Translational andrology and urology · 2022Article
- Vinpocetine SuppressesJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- PDE4 inhibitor rolipram inhibits the expression of microsomal prostaglandin E synthase-1 by a mechanism dependent on MAP kinase phosphatase-1.Pharmacology research & perspectives · 2017Article
- MKP-1 negative regulates Staphylococcus aureus induced inflammatory responses in Raw264.7 cells: roles of PKA-MKP-1 pathway and enhanced by rolipram.Scientific reports · 2017Article
- Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen.Virulence · 2017Article
- Curcumin Inhibits NTHi-Induced MUC5AC Mucin Overproduction in Otitis Media via Upregulation of MAPK Phosphatase MKP-1.International journal of inflammation · 2017Article
- Resveratrol suppresses NTHi-induced inflammation via up-regulation of the negative regulator MyD88 short.Scientific reports · 2016Article
- Dexamethasone modulation of MUC5AC and MUC2 gene expression in a generalized model of middle ear inflammation.The Laryngoscope · 2016Article
- Anti-Inflammatory Effects of β2-Receptor Agonists Salbutamol and Terbutaline Are Mediated by MKP-1.PloS one · 2016Article
- Vinpocetine inhibits Streptococcus pneumoniae-induced upregulation of mucin MUC5AC expression via induction of MKP-1 phosphatase in the pathogenesis of otitis media.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Effect of p38 mitogen-activate protein kinase on MUC5AC protein expression of bile duct epithelial cells in hepatolithiasis patients.International journal of clinical and experimental pathology · 2015Article
- Article
- CYLD negatively regulates nontypeable Haemophilus influenzae-induced IL-8 expression via phosphatase MKP-1-dependent inhibition of ERK.PloS one · 2014Article
- Article
- A mouse model of otitis media identifies HB-EGF as a mediator of inflammation-induced mucosal proliferation.PloS one · 2014Article
- Attenuation of TNF production and experimentally induced inflammation by PDE4 inhibitor rolipram is mediated by MAPK phosphatase-1.British journal of pharmacology · 2013Article
- Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD.Nature communications · 2013Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Otitis media (OM) is the most common childhood bacterial infection and the major cause of conductive hearing loss in children. Mucus overproduction is a hallmark of OM. Streptococcus pneumoniae is the most common gram-positive bacterial pathogen causing OM. Among many mucin genes, MUC5AC has been found to be greatly up-regulated in the middle ear mucosa of human patients with OM. We previously reported that S. pneumoniae up-regulates MUC5AC expression in a MAPK ERK-dependent manner. We also found that MAPK phosphatase-1 (MKP-1) negatively regulates S. pneumoniae-induced ERK-dependent MUC5AC up-regulation. Therapeutic strategies for up-regulating the expression of negative regulators such as MKP-1 may have significant therapeutic potential for treating mucus overproduction in OM. However, the underlying molecular mechanism by which MKP-1 expression is negatively regulated during S. pneumoniae infection is unknown. In this study we show that phosphodiesterase 4B (PDE4B) mediates S. pneumoniae-induced MUC5AC up-regulation by inhibiting the expression of a negative regulator MKP-1, which in turn leads to enhanced MAPK ERK activation and subsequent up-regulation of MUC5AC. PDE4B inhibits MKP-1 expression in a cAMP-PKA-dependent manner. PDE4-specific inhibitor rolipram inhibits S. pneumoniae-induced MUC5AC up-regulation both in vitro and in vivo. Moreover, we show that PDE4B plays a critical role in MUC5AC induction. Finally, topical and post-infection administration of rolipram into the middle ear potently inhibited S. pneumoniae-induced MUC5AC up-regulation. Collectively, these data demonstrate that PDE4B mediates ERK-dependent up-regulation of mucin MUC5AC by S. pneumoniae by inhibiting cAMP-PKA-dependent MKP-1 pathway. This study may lead to novel therapeutic strategy for inhibiting mucus overproduction.
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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.