The lectin-like domain of TNF protects from listeriolysin-induced hyperpermeability in human pulmonary microvascular endothelial cells — A crucial role for protein kinase C-α inhibition
Copyright policy )The lectin-like domain of TNF protects from listeriolysin-induced hyperpermeability in human pulmonary microvascular endothelial cells — A crucial role for protein kinase C-α inhibition
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 LLO-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.
- Harvard University United States
- Institute of Medical Microbiology and Hygiene Germany
- Georgia Regents University United States
- Justus Liebig University Giessen Germany
- Beth Israel Deaconess Medical Center United States
Myosin Light Chains, Protein Kinase C-alpha, Sheep, Tumor Necrosis Factor-alpha, Bacterial Toxins, Pulmonary Artery, Listeria monocytogenes, Permeability, Hemolysin Proteins, Animals, Humans, Cattle, Endothelium, Vascular, Phosphorylation, Peptides, Reactive Oxygen Species, rhoA GTP-Binding Protein, Lung, Cells, Cultured, Heat-Shock Proteins
Myosin Light Chains, Protein Kinase C-alpha, Sheep, Tumor Necrosis Factor-alpha, Bacterial Toxins, Pulmonary Artery, Listeria monocytogenes, Permeability, Hemolysin Proteins, Animals, Humans, Cattle, Endothelium, Vascular, Phosphorylation, Peptides, Reactive Oxygen Species, rhoA GTP-Binding Protein, Lung, Cells, Cultured, Heat-Shock Proteins
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