ArticleBritish journal of pharmacology2012
β-Adrenergic receptors stimulate interleukin-6 production through Epac-dependent activation of PKCδ/p38 MAPK signalling in neonatal mouse cardiac fibroblasts.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Zinc-Releasing Fibrous Scaffolds Modulate Fibroblast, Endothelial, and Macrophage Interactions for Vascularized Tissue Engineering.ACS applied materials & interfaces · 2026Article
- Adrb2 Expression in Ocular-Infiltrating Macrophages Is Necessary for Interleukin-6 Expression and Choroidal Neovascularization.Investigative ophthalmology & visual science · 2025Article
- Miglustat ameliorates isoproterenol-induced cardiac fibrosis via targeting UGCG.Molecular medicine (Cambridge, Mass.) · 2025Article
- Beta-adrenergic stimulation promotes an endoplasmic reticulum stress-dependent inflammatory program in salivary gland epithelial cells.Clinical and experimental immunology · 2024Article
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- CXCR4-dependent macrophage-to-fibroblast signaling contributes to cardiac diastolic dysfunction in heart failure with preserved ejection fraction.International journal of biological sciences · 2022Article
- Role and Mechanism of PKC-δ for Cardiovascular Disease: Current Status and Perspective.Frontiers in cardiovascular medicine · 2022Review
- βLung · 2021Article
- Sympatho-adrenergic mechanisms in heart failure: new insights into pathophysiology.Medical review (2021) · 2021Article
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- Forskolin eye drops improve retinal damage from ischemia/reperfusion.Molecular vision · 2021Article
- G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases.Frontiers in immunology · 2021Review
- Role of the Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy.International journal of molecular sciences · 2020Review
- β2-Adrenergic Receptors Increase Cardiac Fibroblast Proliferation Through the Gαs/ERK1/2-Dependent Secretion of Interleukin-6.International journal of molecular sciences · 2020Article
- Beta-Adrenergic Blockers as a Potential Treatment for COVID-19 Patients.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Article
- Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation.Circulation research · 2020Review
- Effects of β-Adrenergic Blockade on Metabolic and Inflammatory Responses in a Rat Model of Ischemic Stroke.Cells · 2020Article
- β2-adrenergic stimulation induces interleukin-6 by increasing Arid5a, a stabilizer of mRNA, through cAMP/PKA/CREB pathway in cardiac fibroblasts.Pharmacology research & perspectives · 2020Article
- βBritish journal of pharmacology · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND PURPOSE IL-6 plays crucial roles in cardiac hypertrophy, cardiac fibrosis and heart failure. Activation of β-adrenoceptors induced IL-6 production in neonatal mouse cardiac fibroblasts (NMCFs) through a G(s) /adenylate cyclase/cAMP/p38 MAPK pathway but independent of PKA. However, how cAMP activates p38 MAPK is still not defined. In this study, we have assessed the role of the exchange protein directly activated by cAMP (Epac) and PKCδ in p38 MAPK activation and IL-6 production by stimulated by the β-adrenoceptor agonist isoprenaline in NMCFs. EXPERIMENTAL APPROACH The IL-6 concentration in cell culture supernatants was measured by ELISA. The levels of phosphorylated and total p38 MAPK and PKCδ were determined by Western blot analysis. The translocation of PKCδ was determined by immunoblotting the soluble and particulate fractions. Expression of Epac1 or PKCδ was knocked down by the corresponding, adenovirus-mediated, small hairpin RNA (shRNA). RESULTS In NMCFs, activation of β-adrenoceptors enhanced PKCδ phosphorylation and translocation. Furthermore, knock-down of the PKCδ isoform using an adenovirus-mediated shRNA markedly down-regulated IL-6 induction by NMCFs stimulated with isoprenaline. Moreover, knock-down of Epac1 confirmed that Epac1 was upstream of PKCδ in IL-6 production. Additionally, both Epac1 and PKCδ mediated the p38 MAPK activation induced by isoprenaline. CONCLUSIONS AND IMPLICATIONS β-Adrenoceptor agonists activate a cAMP/Epac/PKCδ/p38 MAPK pathway to produce IL-6 in NMCFs. This study identifies Epac as the link between cAMP and p38 MAPK signalling pathways and demonstrates that PKCδ can function as a novel downstream effector of this β-adrenoceptor/cAMP/Epac pathway.
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