ArticleJournal of neuroinflammation2018
Protein kinase C-delta inhibition protects blood-brain barrier from sepsis-induced vascular damage.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- Protein Kinase C-delta (PKCδ) in Neurodegeneration and Cerebral Ischemia: Molecular Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- A biomimetic microphysiological system predicts the impact of sepsis therapeutics on neutrophil-endothelial dynamics.Lab on a chip · 2026Article
- Bone marrow-derived mesenchymal stem cells for ischemic stroke: mechanisms, delivery strategies, clinical evidence, and translational challenges.Stem cell research & therapy · 2026Review
- Strategies for blood-brain barrier rejuvenation and repair.Nature reviews. Drug discovery · 2026Review
- Protein Kinase C-Delta (PKCδ) inhibition stabilizes endothelium and suppresses triple-negative breast cancer (TNBC) intravasation in a microfluidic hypoxic tumor model.Bioengineering & translational medicine · 2026Article
- Dysregulation of Neutrophil-Endothelial Communication in Sepsis: Mechanisms and Therapeutic Perspectives.Cells · 2026Review
- Extracellular matrix anchored neutrophils drive pulmonary fibrosis in mice.Nature communications · 2025Article
- Developing a Human Immune-Endothelial Coculture Model for Inflammatory Vasculitis and Drug Screening.ACS omega · 2025Article
- Prioritizing FDA approved therapeutics for treating sepsis phenotypes: A network modeling approach based on neutrophil proteomics.Frontiers in immunology · 2025Article
- Distinct functional neutrophil phenotypes in sepsis patients correlate with disease severity.Frontiers in immunology · 2024Article
- PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023Review
- Biomimetic on-chip assay reveals the anti-metastatic potential of a novel thienopyrimidine compound in triple-negative breast cancer cell lines.Frontiers in bioengineering and biotechnology · 2023Article
- The critical role of neutrophil-endothelial cell interactions in sepsis: new synergistic approaches employing organ-on-chip, omics, immune cell phenotyping andFrontiers in cellular and infection microbiology · 2023Review
- β-Glucosylceramides and Tocopherols Regulate Development and Function of Dendritic Cells.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Transcranial ultrasound diagnostic value of hemodynamic cerebral changes in preterm infants for early-onset sepsis.Translational pediatrics · 2022Article
- Cerebral malaria - modelling interactions at the blood-brain barrier in vitro.Disease models & mechanisms · 2022Review
- Inhibition of PKC-δ reduce rhabdomyolysis-induced acute kidney injury.Journal of cellular and molecular medicine · 2022Article
- Post-stroke Impairment of the Blood-Brain Barrier and Perifocal Vasogenic Edema Is Alleviated by Endovascular Mesenchymal Stem Cell Administration: Modulation of the PKCδ/MMP9/AQP4-Mediated Pathway.Molecular neurobiology · 2022Article
- Sepsis-associated neuroinflammation in the spinal cord.PloS one · 2022Article
- Emerging Trends and Hot Spots in Sepsis-Associated Encephalopathy Research From 2001 to 2021: A Bibliometric Analysis.Frontiers in medicine · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNeuroinflammation often develops in sepsis leading to activation of cerebral endothelium, increased permeability of the blood-brain barrier (BBB), and neutrophil infiltration. We have identified protein kinase C-delta (PKCδ) as a critical regulator of the inflammatory response and demonstrated that pharmacologic inhibition of PKCδ by a peptide inhibitor (PKCδ-i) protected endothelial cells, decreased sepsis-mediated neutrophil influx into the lung, and prevented tissue damage. The objective of this study was to elucidate the regulation and relative contribution of PKCδ in the control of individual steps in neuroinflammation during sepsis.
methodsThe role of PKCδ in mediating human brain microvascular endothelial (HBMVEC) permeability, junctional protein expression, and leukocyte adhesion and migration was investigated in vitro using our novel BBB on-a-chip (B
resultsDuring sepsis, PKCδ is activated in the rat brain resulting in membrane translocation, a step that is attenuated by treatment with PKCδ-i. Similarly, TNF-α-mediated activation of PKCδ and its translocation in HBMVEC are attenuated by PKCδ-i in vitro. PKCδ inhibition significantly reduced TNF-α-mediated hyperpermeability and TEER decrease in vitro in activated HBMVEC and rat brain in vivo 24 h after CLP induced sepsis. TNF-α-treated HBMVEC showed interrupted tight junction expression, whereas continuous expression of tight junction protein was observed in non-treated or PKCδ-i-treated cells. PKCδ inhibition also reduced TNF-α-mediated neutrophil adhesion and migration across HBMVEC in B
conclusionsThe BBB on-a-chip (B
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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.