title: The lectin-like domain of TNF protects from listeriolysin-induced hyperpermeability in human pulmonary microvascular endothelial cells - a crucial role for protein kinase C-alpha inhibition.
abstract: 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.
authors.affiliation: Medical College of Georgia, Augusta, GA, USA.
authors.forename: Chenling
authors.initials: C
authors.lastname: Xiong
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Kumar
authors.forename: Saurabh
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Martin
authors.initials: M
authors.lastname: Leustik
authors.forename: Connie
authors.initials: C
authors.lastname: Snead
authors.forename: Juerg
authors.initials: J
authors.lastname: Hamacher
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fischer
authors.forename: Nagavedi S
authors.initials: NS
authors.lastname: Umapathy
authors.forename: Hamid
authors.initials: H
authors.lastname: Hossain
authors.forename: Albrecht
authors.initials: A
authors.lastname: Wendel
authors.forename: John D
authors.initials: JD
authors.lastname: Catravas
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Verin
authors.forename: David
authors.initials: D
authors.lastname: Fulton
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Black
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Rudolf
authors.initials: R
authors.lastname: Lucas
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000382:microbiology; D006360:Heat-Shock Proteins / Q000633:toxicity*; D006460:Hemolysin Proteins / Q000633:toxicity*; D006801:Humans; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D018994:Myosin Light Chains / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010539:Permeability; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors; D011651:Pulmonary Artery / Q000378:metabolism / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D018994:Myosin Light Chains; D010455:Peptides; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C521715:pepBs1-Ac peptide; D051571:Protein Kinase C-alpha; D020742:rhoA GTP-Binding Protein; C038705:hlyA protein, Listeria monocytogenes