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Updated: Mar 1, 2026
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A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
Published on: December 9, 2021
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Protein kinase C-alpha mediates endothelial barrier dysfunction induced by TNF-alpha
T Ferro1, P Neumann, N Gertzberg
1Research Service, Stratton Veterans Affairs Medical Center, Albany Medical College, New York 12208, USA.
Summary
Protein kinase C-alpha (PKC-alpha) mediates tumor necrosis factor-alpha (TNF-alpha)-induced increases in pulmonary endothelial permeability. Blocking PKC-alpha prevents TNF-alpha
Area of Science:
- Endothelial biology
- Molecular signaling
- Pulmonary vascular research
Background:
- Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory cytokine.
- Endothelial barrier dysfunction contributes to inflammatory lung diseases.
- The role of protein kinase C-alpha (PKC-alpha) in TNF-alpha-induced endothelial permeability is not fully understood.
Purpose of the Study:
- To investigate the role of PKC-alpha in TNF-alpha-induced pulmonary microvessel endothelial cell (PEM) permeability.
- To determine if PKC-alpha activation is necessary for TNF-alpha to increase endothelial permeability.
Main Methods:
- Assessed PEM permeability using albumin clearance.
- Measured PKC-alpha mRNA, protein, and activity in PEM lysates.
- Utilized PKC-alpha antisense oligonucleotides and specific PKC inhibitors (myristoylated protein kinase C inhibitor, calphostin).
Main Results:
- TNF-alpha increased PKC-alpha protein, activity, and PEM permeability.
- PKC-alpha antisense oligonucleotides prevented TNF-alpha-induced increases in protein, activity, and permeability.
- PKC inhibitors blocked TNF-alpha-induced permeability increases, even when administered after TNF-alpha exposure.
Conclusions:
- PKC-alpha activation is a critical mediator of TNF-alpha-induced pulmonary endothelial barrier dysfunction.
- Prolonged PKC-alpha activation, sustained by de novo protein synthesis, underlies TNF-alpha effects.
- Targeting PKC-alpha may offer therapeutic strategies for inflammatory lung conditions.
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