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Updated: Mar 17, 2026

A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
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Regulation of Thrombin-Induced Lung Endothelial Cell Barrier Disruption by Protein Kinase C Delta

Lishi Xie1,2, Eddie T Chiang3, Xiaomin Wu3

  • 1Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.

Plos One
|July 22, 2016
PubMed

Insights

Protein Kinase C delta (PKCδ) worsens endothelial cell barrier dysfunction during thrombin exposure. This isoform regulates cytoskeleton dynamics, offering a potential therapeutic target for lung injury and sepsis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • Protein Kinase C (PKC) isozymes regulate endothelial cell (EC) barrier function.
  • Understanding specific PKC isoform roles in vascular homeostasis is crucial.

Purpose of the Study:

  • To elucidate the role of the PKCδ isoform in thrombin-induced loss of human pulmonary artery EC barrier integrity.
  • To identify downstream signaling pathways regulated by PKCδ in ECs.

Main Methods:

  • Inhibitory studies using rottlerin.
  • Expression of dominant-negative PKCδ construct.
  • PKCδ silencing via siRNA.
  • Assessment of MLC phosphorylation and Rho GTPase activation.
  • Analysis of cytoskeleton rearrangement and EC barrier function.

Main Results:

  • PKCδ isoform was identified as a key mediator promoting thrombin-induced EC barrier loss.
  • PKCδ activation positively feedbacks on Rho GTPase and inhibits Rac1 GTPase.
  • PKCδ targets, PKD (PKCμ) and CPI-17, were activated and modulated EC cytoskeleton.

Conclusions:

  • PKCδ plays a critical role in regulating EC cytoskeleton and barrier integrity.
  • PKCδ is a potential therapeutic target for inflammatory lung disorders like acute lung injury and sepsis.

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