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 Citations (Scopus)

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 1 2010

Fingerprint

Lectins
Protein Kinase C
Myosin Light Chains
Endothelial Cells
Lung
Permeability
Reactive Oxygen Species
Phosphorylation
Listeriosis
Protein C Inhibitor
Listeria monocytogenes
Virulence Factors
Protein Kinase Inhibitors
Edema
Newborn Infant
Cytokines
Peptides
Listeria monocytogenes hlyA protein
In Vitro Techniques
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

Cite this

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

In: Vascular Pharmacology, Vol. 52, No. 5-6, 01.05.2010, p. 207-213.

Research output: Contribution to journalArticle

Xiong, Chenling ; Yang, Guang ; Kumar, Sanjiv ; Aggarwal, Saurabh ; Leustik, Martin ; Snead, Connie ; Hamacher, Juerg ; Fischer, Bernhard ; Siddaramappa, Umapathy N ; Hossain, Hamid ; Wendel, Albrecht ; Catravas, John D. ; Verin, Alexander Dmitriyevich ; Fulton, David J ; Black, Stephen Matthew ; Chakraborty, Trinad ; Lucas, Rudolf. / 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. In: Vascular Pharmacology. 2010 ; Vol. 52, No. 5-6. pp. 207-213.
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