ArticleBritish journal of pharmacology2013
Attenuation of TNF production and experimentally induced inflammation by PDE4 inhibitor rolipram is mediated by MAPK phosphatase-1.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Dexamethasone regulates gene expression in chondrocytes through MKP-1 and downregulates cholesterol hydroxylases CH25H and CYP7B1.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Rolipram prevents detrusor underactivity related to pelvic nerve injury in rats by promoting regeneration of nerve axons.World journal of urology · 2025Article
- Screening of the FDA-approved drug library identifies CCL17 inhibitors that block arthritic pain.Scientific reports · 2025Article
- Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- MKP-1 Deficiency Exacerbates Skin Fibrosis in a Mouse Model of Scleroderma.International journal of molecular sciences · 2023Article
- TRPA1 as a potential factor and drug target in scleroderma: dermal fibrosis and alternative macrophage activation are attenuated in TRPA1-deficient mice in bleomycin-induced experimental model of scleroderma.Arthritis research & therapy · 2023Article
- Salicylate Sodium Suppresses Monocyte Chemoattractant Protein-1 Production by Directly Inhibiting Phosphodiesterase 3B in TNF-α-Stimulated Adipocytes.International journal of molecular sciences · 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
- Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1.International journal of molecular sciences · 2022Article
- p38 MAPK Endogenous Inhibition Improves Neurological Deficits in Global Cerebral Ischemia/Reperfusion Mice.Neural plasticity · 2022Article
- Article
- Protective effects of rolipram on endotoxic cardiac dysfunction via inhibition of the inflammatory response in cardiac fibroblasts.BMC cardiovascular disorders · 2020Article
- The p38/MKP-1 signaling axis in oral cancer: Impact of tumor-associated macrophages.Oral oncology · 2020Review
- Rolipram Protects Mice from Gram-negative Bacterium Escherichia coli-induced Inflammation and Septic Shock.Scientific reports · 2020Article
- Article
- Phosphodiesterase 4 and 7 inhibitors produce protective effects against high glucose-induced neurotoxicity in PC12 cells via modulation of the oxidative stress, apoptosis and inflammation pathways.Metabolic brain disease · 2018Article
- Inhibition of proinflammatory pathways by bioactive fraction of Tinospora cordifolia.Inflammopharmacology · 2018Article
- 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
- Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice.Laboratory investigation; a journal of technical methods and pathology · 2017Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purpose3',5'-Cyclic nucleotide PDE4 is expressed in several inflammatory and immune cells, and PDE4 catalyses the hydrolysis of cAMP to 5'AMP, down-regulating cAMP signalling in cells. MAPK phosphatase-1 (MKP-1) is an endogenous p38 MAPK signalling suppressor and limits inflammatory gene expression and inflammation. In the present study, we investigated the effect of a PDE4 inhibitor rolipram on MKP-1 expression and whether MKP-1 is involved in the anti-inflammatory effects of rolipram. EXPERIMENTAL APPROACH: The effect of rolipram on TNF production was investigated in J774 mouse macrophage cell line and in primary mouse peritoneal macrophages (PM) from wild-type (WT) and MKP-1(-/-) mice. We also investigated the effect of rolipram on carrageenan-induced paw inflammation in WT and MKP-1(-/-) mice. KEY
resultsMKP-1 expression was enhanced by rolipram, by a non-selective PDE inhibitor IBMX and by a cAMP analogue 8-Br-cAMP in J774 cells and in PM. Enhanced MKP-1 mRNA expression by rolipram was reversed by a PKA inhibitor. Rolipram, IBMX and 8-Br-cAMP also inhibited TNF production in activated macrophages. Accordingly, rolipram inhibited TNF production in PMs from WT mice but, interestingly, not in PMs from MKP-1(-/-) mice. Furthermore, rolipram attenuated carrageenan-induced paw inflammation in WT but not in MKP-1(-/-) mice. CONCLUSIONS AND IMPLICATIONS: PDE4 inhibitor rolipram was found to enhance the expression of MKP-1, and MKP-1 mediated, at least partly, the anti-inflammatory effects of PDE4 inhibition. The results suggest that compounds that enhance MKP-1 expression and/or MKP-1 activity hold potential as novel anti-inflammatory drugs.
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