Journal
VASCULAR PHARMACOLOGY
Volume 52, Issue 5-6, Pages 207-213Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2009.12.010
Keywords
Listeriolysin; Endothelial hyperpermeability; TNF; Protein kinase C; Reactive oxygen species
Categories
Funding
- BMBF-Clinical Research Group in Infectious Diseases
- BMBF
- Apeptico, Vienna, Austria
- Cardiovascular Discovery Institute of the Medical College of Georgia
- [HL67841]
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Listeriosis can lead to potentially lethal pulmonary complications in newborns and immune compromised patients, characterized by extensive permeability edema. Listeriolysin (LLO), the main virulence factor of Listeria monocytogenes, induces a dose-dependent hyperpermeability in monolayers of human lung microvascular endothelial cells in vitro. The permeability increasing activity of LLO, which is accompanied by an increased reactive oxygen species (ROS) generation, RhoA activation and myosin light chain (MLC) phosphorylation, can be completely inhibited by the protein kinase C (PKC) alpha/beta inhibitor GO6976, indicating a crucial role for PKC in the induction of barrier dysfunction. The TNF-derived TIP peptide, which mimics the lectin-like domain of the cytokine, blunts LLO-induced hyperpermeability in vitro, upon inhibiting LLD-induced protein kinase C-alpha activation, ROS generation and MLC phosphorylation and upon restoring the RhoA/Rac 1 balance. These results indicate that the lectin-like domain of TNF has a potential therapeutic value in protecting from LLO-induced pulmonary endothelial hyperpermeability. (C) 2010 Elsevier Inc. All rights reserved.
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