Effect of tryptase on mouse brain microvascular endothelial cells via protease-activated receptor 2

Qin Zhou1, Yi-Wei Wang1, Peng-Fei Ni1

  • 1Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.

Abstract

Insights

Mast cells release tryptase, which activates brain endothelial cells via PAR-2, disrupting the blood-brain barrier (BBB). This study clarifies tryptase

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Mast cells (MCs) are key in brain injury, potentially disrupting the blood-brain barrier (BBB).
  • Tryptase, an abundant MC product, interacts with Protease-activated receptor 2 (PAR-2) on brain microvascular endothelial cells, crucial for BBB integrity.
  • The precise mechanism of MC-induced BBB disruption requires elucidation.

Purpose of the Study:

  • To investigate the effects of tryptase on mouse brain microvascular endothelial cells (bEnd3).
  • To explore the potential mechanisms underlying tryptase-induced changes in these cells.

Main Methods:

  • Examined tryptase-induced activation of mouse brain microvascular endothelial cells.
  • Assessed cellular activation, cytokine production, and pathway signaling (MAPK, NF-κB) after PAR-2 antagonism and tryptase stimulation.

Main Results:

  • Tryptase increased VCAM-1, MMPs, TLR4, and TNF-α, while decreasing tight junction proteins (occludin, claudin-5).
  • Tryptase activated ERK and NF-κB signaling pathways.
  • PAR-2 inhibition abolished these tryptase-induced effects.

Conclusions:

  • Tryptase activates brain microvascular endothelial cells and promotes pro-inflammatory mediator release.
  • These findings elucidate the mechanism of tryptase in blood-brain barrier disruption.

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