ArticleShock (Augusta, Ga.)2019
Protein Kinase C-Delta (PKCδ) Tyrosine Phosphorylation is a Critical Regulator of Neutrophil-Endothelial Cell Interaction in Inflammation.
Article in Shock (Augusta, Ga.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Glycyrrhizic acid attenuates sepsis-induced acute lung injury by regulating macrophage M2 polarization via PRKCD.Journal of thoracic disease · 2026Article
- 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
- Electroacupuncture reduces calcium influx and inhibits endoplasmic reticulum stress by inhibiting the PKCδ-TRPA1 pathway to promote motor function recovery after spinal cord injury.Burns & trauma · 2026Article
- NETosis-specific cell death: a novel mechanism in the pathogenesis of gouty arthritis.European journal of medical research · 2025Review
- Article
- Analyzing the molecular mechanism of Scutellaria Radix in the treatment of sepsis using RNA sequencing.BMC infectious diseases · 2024Article
- Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential.Journal of inflammation research · 2024Review
- Protein kinase C delta regulates mononuclear phagocytes and hinders response to immunotherapy in cancer.Science advances · 2023Article
- 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 therapeutic effect of adipose-derived stem cells on soft tissue injury after radiotherapy and their value for breast reconstruction.Stem cell research & therapy · 2022Review
- Review
- Inhibition of PKC-δ reduce rhabdomyolysis-induced acute kidney injury.Journal of cellular and molecular medicine · 2022Article
- The interaction of MD-2 with small molecules in huanglian jiedu decoction play a critical role in the treatment of sepsis.Frontiers in pharmacology · 2022Article
- Impaired respiratory burst contributes to infections in PKCδ-deficient patients.The Journal of experimental medicine · 2021Article
- Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics.International journal of molecular sciences · 2021Review
- Mechanisms of radiation-induced endothelium damage: Emerging models and technologies.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2021Review
- Experimental Approaches to Evaluate Leukocyte-Endothelial Cell Interactions in Sepsis and Inflammation.Shock (Augusta, Ga.) · 2020Article
- Protein kinase C-delta inhibition is organ-protective, enhances pathogen clearance, and improves survival in sepsis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- A specific small-molecule inhibitor of protein kinase CδI activity improves metabolic dysfunction in human adipocytes from obese individuals.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNeutrophil dysfunction plays an important role in inflammation-induced tissue injury. Previously, we identified protein kinase C-δ (PKCδ) as a critical controller of neutrophil activation and trafficking but how PKCδ is regulated in inflammation has not been delineated. PKCδ activity is regulated by tyrosine phosphorylation on multiple sites. Tyrosine155 is a key regulator of apoptosis and gene expression, but its role in proinflammatory signaling is not known.
methodsIn-vitro studies - superoxide anion (O2) and neutrophil extracellular traps (NETs) were measured in bone marrow neutrophils (BMN) isolated from wild type (WT) and PKCδY155F knock-in mice (PKCδ tyrosine 155 → phenylalanine). Our novel 3D biomimetic microfluidic assay (bMFA) was used to delineate PKCδ-mediated regulation of individual steps in neutrophil adhesion and migration using WT and PKCδY155F BMN and mouse lung microvascular endothelial cells (MLMVEC). In-vivo studies - WT and PKCδY155F knock-in mice underwent sham or cecal ligation and puncture surgery and the lungs harvested 24 h post-surgery.
resultsIn vitro - PKCδY155F BMN had significantly reduced O2 and NETs release compared with WT. WT BMN, but not PKCδY155F BMN, demonstrated significant adhesion and migration across tumor necrosis factor-activated MLMVEC in bMFA. PKCδ inhibition significantly reduced WT BMN adhesion and migration under low shear and near bifurcations, but had no effect on PKCδY155F BMN. In vivo - mutation of PKCδ tyrosine 155 significantly decreased neutrophil migration into the lungs of septic mice.
conclusionsPKCδ tyrosine 155 is a key phosphorylation site controlling proinflammatory signaling and neutrophil-endothelial cell interactions. These studies provide mechanistic insights into PKCδ regulation during inflammation.
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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.