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

Chenling Xiong, Guang Yang, Sanjiv Kumar, Saurabh Aggarwal, Martin Leustik, Connie Snead, Juerg Hamacher, Bernhard Fischer, Umapathy N Siddaramappa, Hamid Hossain, Albrecht Wendel, John D. Catravas, Alexander Dmitriyevich Verin, David J Fulton, Stephen Matthew Black, Trinad Chakraborty, Rudolf Lucas

Research output: Contribution to journalArticle

23 Scopus citations

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) α/β inhibitor GÖ6976, 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-α 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.

Original languageEnglish (US)
Pages (from-to)207-213
Number of pages7
JournalVascular Pharmacology
Volume52
Issue number5-6
DOIs
StatePublished - May 2010

Keywords

  • Endothelial hyperpermeability
  • Listeriolysin
  • Protein kinase C
  • Reactive oxygen species
  • TNF

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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