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On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
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Preconditioning with endoplasmic reticulum stress ameliorates endothelial cell inflammation
Antony Leonard1, Adrienne W Paton2, Monaliza El-Quadi1
1Department of Pediatrics, Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
Plos One
|October 31, 2014
Summary
Endoplasmic Reticulum (ER) stress impacts endothelial cell inflammation. Reducing BiP function alleviates inflammation and restores endothelial barrier integrity, suggesting BiP
Area of Science:
- Cell Biology
- Molecular Biology
- Pathophysiology
Background:
- Endoplasmic Reticulum (ER) stress disrupts cellular homeostasis and is linked to various diseases.
- ER stress is increasingly recognized for its role in inflammatory conditions.
- Endothelial cell (EC) inflammation is a key factor in acute lung injury (ALI) pathogenesis.
Purpose of the Study:
- To investigate the role of ER stress in endothelial cell (EC) inflammation.
- To understand how ER stress influences the pathogenesis of acute lung injury (ALI).
Main Methods:
- Utilized siRNA to deplete BiP (ER chaperone) in human pulmonary artery endothelial cells (HPAAPCs).
- Employed subtilase cytotoxin (SubAB) to inactivate BiP in HPAAPCs.
- Assessed NF-κB activation, IκBα degradation, and endothelial barrier integrity.
Main Results:
- Depleting or inactivating BiP reduced EC inflammation and restored endothelial barrier integrity.
- BiP modulation induced ER stress markers (ATF4, p-eIF2α) and blunted NF-κB activation.
- BiP siRNA inhibited thrombin-induced NF-κB signaling, while SubAB interfered with NF-κB DNA binding.
Conclusions:
- BiP plays a critical role in EC inflammation and injury.
- Modulating BiP function offers a potential therapeutic strategy for ALI.
- Targeting BiP impacts NF-κB signaling and vascular permeability.
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