Related Experiment Video
Updated: Feb 5, 2026

Isolation of Primary Murine Brain Microvascular Endothelial Cells
Published on: November 14, 2014
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.
Background:
Mast cells (MCs), the 'first responders' in brain injury, are able to disrupt the blood-brain barrier (BBB), but the underlying mechanism is not well understood. Tryptase is the most abundant MC secretory product. Protease-activated receptor 2 (PAR-2) has been identified as a specific receptor for tryptase, which is abundantly expressed in brain microvascular endothelial cells. The BBB comprises brain microvascular endothelial cells that display specialised molecular properties essential for BBB function and integrity. Therefore, the purpose of the present study was to investigate the effects of tryptase on mouse brain microvascular endothelial cell line bEnd3 and its potential mechanisms of action.
Methods:
Induction of mouse brain microvascular endothelial cell activation by tryptase was examined. Then, mouse brain microvascular endothelial cells were pretreated with a PAR-2 antagonist and stimulated with tryptase. Cellular activation, proinflammatory cytokine production, expression of PAR-2, Toll-like receptors (TLRs) and mitogen-activated protein kinases (MAPK), nuclear factor kappa B (NF-kappa B) phosphorylation were assessed.
Results:
Tryptase upregulated the production of VCAM-1, MMPs (MMP9 and MMP2), TLR4 and TNF-α and downregulated the expression of the tight junction proteins occludin and claudin-5 in mouse brain microvascular endothelial cell. Among the MAPK and NF-kappa B pathway, ERK and NF-kappa B were activated by tryptase. All of these effects could be eliminated by the PAR-2 inhibitor.
Conclusion:
Based on our findings, we conclude that tryptase can trigger brain microvascular endothelial cell activation and proinflammatory mediator release. These findings may further clarify the involvement and mechanism of tryptase in BBB disruption.
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.
Related Concept Videos
Internal Receptors
Types of Receptors: Cell Surface Receptors
Receptor-mediated Endocytosis
Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
G-protein Coupled Receptors
Co-activators and Co-repressors

