ArticleThe Journal of biological chemistry2014
Protein kinase C-δ (PKCδ) regulates proinflammatory chemokine expression through cytosolic interaction with the NF-κB subunit p65 in vascular smooth muscle cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
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- Hypoxia-Induced Inflammation in In Vitro Model of Human Blood-Brain Barrier: Modulatory Effects of the Olfactory Ensheathing Cell-Conditioned Medium.Molecular neurobiology · 2025Article
- PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases.Frontiers in immunology · 2024Review
- The Role of the NF-kB Pathway in Intracranial Aneurysms.Brain sciences · 2023Review
- Identification of Potential Abnormal Methylation-Modified Genes in Coronary Artery Ectasia.International journal of genomics · 2023Article
- CCL7 as a novel inflammatory mediator in cardiovascular disease, diabetes mellitus, and kidney disease.Cardiovascular diabetology · 2022Review
- Endoplasmic reticulum stress contributes to cisplatin-induced chronic kidney disease via the PERK-PKCδ pathway.Cellular and molecular life sciences : CMLS · 2022Article
- Intermediate monocytes induced by IFN-γ inhibit cancer metastasis by promoting NK cell activation through FOXO1 and interleukin-27.Journal for immunotherapy of cancer · 2022Article
- Plasmalogens and Chronic Inflammatory Diseases.Frontiers in physiology · 2021Review
- Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected withJournal of fungi (Basel, Switzerland) · 2020Article
- In vitro anti-inflammatory effects of curcumin on mast cell-mediated allergic responses via inhibiting FcεRI protein expression and protein kinase C delta translocation.Cytotechnology · 2020Article
- 99-Case Study of Sporadic Aortic Dissection by Whole Exome Sequencing Indicated Novel Disease-Associated Genes and Variants in Chinese Population.BioMed research international · 2020Article
- PKCδ Mediates NF-κB Inflammatory Response and Downregulates SIRT1 Expression in Liver Fibrosis.International journal of molecular sciences · 2019Article
- Endothelial or vascular smooth muscle cell-specific expression of human NOX5 exacerbates renal inflammation, fibrosis and albuminuria in the Akita mouse.Diabetologia · 2019Article
- G Protein α Subunit 14 Mediates Fibroblast Growth Factor 2-Induced Cellular Responses in Human Endothelial Cells.Journal of cellular physiology · 2019Article
- Inhibition of IL-13 and IL-13Rα2 Expression by IL-32θ in Human Monocytic Cells Requires PKCδ and STAT3 Association.International journal of molecular sciences · 2019Article
- Novel Paracrine Functions of Smooth Muscle Cells in Supporting Endothelial Regeneration Following Arterial Injury.Circulation research · 2019Article
- Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium.Nature biomedical engineering · 2019Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Proinflammatory chemokines released by vascular smooth muscle cells (VSMCs) play a critical role in vascular inflammation. Protein kinase C-δ (PKCδ) has been shown to be up-regulated in VSMCs of injured arteries. PKCδ knock-out (Prkcd(-/-)) mice are resistant to inflammation as well as apoptosis in models of abdominal aortic aneurysm. However, the precise mechanism by which PKCδ modulates inflammation remains incompletely understood. In this study, we identified four inflammatory chemokines (Ccl2/Mcp-1, Ccl7, Cxcl16, and Cx3cl1) of over 45 PKCδ-regulated genes associated with inflammatory response by microarray analysis. Using CCL2 as a prototype, we demonstrated that PKCδ stimulated chemokine expression at the transcriptional level. Inhibition of the NF-κB pathway or siRNA knockdown of subunit p65, but not p50, eliminated the effect of PKCδ on Ccl2 expression. Overexpressing PKCδ followed by incubation with phorbol 12-myristate 13-acetate resulted in an increase in p65 Ser-536 phosphorylation and enhanced DNA binding affinity without affecting IκB degradation or p65 nuclear translocation. Prkcd gene deficiency impaired p65 Ser-536 phosphorylation and DNA binding affinity in response to TNFα. Results from in situ proximity ligation analysis and co-immunoprecipitation performed on cultured VSMCs and aneurysmal aorta demonstrated physical interaction between PKCδ and p65 that took place largely outside the nucleus. Promoting nuclear translocation of PKCδ with peptide ψδRACK diminished Ccl2 production, whereas inhibition of PKCδ translocation with peptide δV1-1 enhanced Ccl2 expression. Together, these results suggest that PKCδ modulates inflammation at least in part through the NF-κB-mediated chemokines. Mechanistically, PKCδ activates NF-κB through an IκB-independent cytosolic interaction, which subsequently leads to enhanced p65 phosphorylation and DNA binding affinity.
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