The role of p38 map kinase in tumor necrosis factor-induced redistribution of vascular endothelial cadherin and increased endothelial permeability

Fiemu E. Nwariaku, Jianping Chang, Xudong Zhu, Zijuan Liu, Steven L. Duffy, Nabil H. Halaihel, Lance Terada, Richard H. Turnage

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

The mechanism by which tumor necrosis factor alpha (TNFα) increases endothelial permeability is unclear. Vascular endothelial (VE) cadherin (cadherin 5) is an important contributor to endothelial monolayer integrity. The purpose of our study was to determine the effect of TNFα on VE-cadherin cell-surface expression and to identify the signaling pathways involved in TNF-induced changes in cadherin expression. Human umbilical vein endothelial cell monolayer permeability was measured by enzyme-linked immunosorbent assay for biotin-labeled albumin. Immunofluorescence, laser confocal microscopy, and Western immunobloting were used to assess VE cadherin distribution. Mitogen-activated protein kinase (MAPK) activity was determined using functional kinase assays and was inhibited with the compounds SB202190 and PD98059. TNFα significantly increased permeability and induced p38 and ERK MAPK activation compared with controls (P < 0.05. These changes were associated with a loss of membrane-associated VE cadherin. Inhibition of p38 but not ERK MAPK significantly reduced the effect of TNFα on endothelial permeability and cell-surface VE cadherin expression. p38 MAP kinase activation appears to be an important upstream signaling event associated with increased endothelial permeability and vascular endothelial cadherin redistribution.

Original languageEnglish (US)
Pages (from-to)82-85
Number of pages4
JournalShock
Volume18
Issue number1
DOIs
StatePublished - Jul 2002

Keywords

  • Adhesion molecules
  • Cytokine signaling
  • Endothelium
  • Mitogen-activated protein kinase
  • Tumor necrosis factor alpha

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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