Cyclooxygenase-2 mediates hydrogen peroxide-induced wound repair in human endothelial cells

Sonia Eligini, Izaskun Arenaz, Silvia S. Barbieri, Maurizio L. Faleri, Mauro Crisci, Elena Tremoli, Susanna Colli

Research output: Contribution to journalArticlepeer-review

Abstract

Cyclooxygenase-2 (Cox-2) metabolites produced by endothelial cells, particularly prostacyclin and prostaglandin E2, profoundly affect vascular tone, regional blood flow, and angiogenesis. We have previously shown that reactive oxygen species induce Cox-2 expression in human endothelial cells (HUVEC), either on their own or as components of the signaling pathway triggered by TNFα, the prototypical inflammatory cytokine. Here we investigated the role of Cox-2 induced by hydrogen peroxide (H2O2), either exogenous or endogenously generated by TNFα, in the repair of a mechanically wounded HUVEC monolayer and probed the sources of H2O2 that are involved in TNFα signaling and the pathways through which H2O2 modulates Cox-2 expression. Results indicate that H2O2-induced Cox-2 activity participates in the repair of wounded monolayers. Both NADPH oxidase and the mitochondrial electron transport chain are involved in H2O2 generation. Signaling triggered by H2O2 for Cox-2 induction acts by increasing the protein tyrosine kinase phosphorylation that follows inhibition of protein phosphatase activity. The activation of p38 MAPK and its interaction in the inhibition of serine/threonine phosphatase activity are both critical steps in this event. We conclude that Cox-2 induced by H2O2 plays an important role in promoting endothelial wound repair after injury, so that the cardioprotective effect of Cox-2 is due at least in part to its power of healing damaged endothelium.

Original languageEnglish
Pages (from-to)1428-1436
Number of pages9
JournalFree Radical Biology and Medicine
Volume46
Issue number10
DOIs
Publication statusPublished - May 15 2009

Keywords

  • Cyclooxygenase-2
  • Endothelial wound
  • Free radicals
  • Hydrogen peroxide
  • p38 MAPK
  • Phosphatases
  • Reactive oxygen species sources

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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