title: Cyclooxygenase-2 mediates hydrogen peroxide-induced wound repair in human endothelial cells.
abstract: Cyclooxygenase-2 (Cox-2) metabolites produced by endothelial cells, particularly prostacyclin and prostaglandin E(2), 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 TNFalpha, the prototypical inflammatory cytokine. Here we investigated the role of Cox-2 induced by hydrogen peroxide (H(2)O(2)), either exogenous or endogenously generated by TNFalpha, in the repair of a mechanically wounded HUVEC monolayer and probed the sources of H(2)O(2) that are involved in TNFalpha signaling and the pathways through which H(2)O(2) modulates Cox-2 expression. Results indicate that H(2)O(2)-induced Cox-2 activity participates in the repair of wounded monolayers. Both NADPH oxidase and the mitochondrial electron transport chain are involved in H(2)O(2) generation. Signaling triggered by H(2)O(2) 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 H(2)O(2) 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.
authors.affiliation: E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Eligini
authors.forename: Izaskun
authors.initials: I
authors.lastname: Arenaz
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Barbieri
authors.forename: Maurizio L
authors.initials: ML
authors.lastname: Faleri
authors.forename: Mauro
authors.initials: M
authors.lastname: Crisci
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.forename: Susanna
authors.initials: S
authors.lastname: Colli
mesh_terms: D002316:Cardiotonic Agents / Q000378:metabolism*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004579:Electron Transport; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology; D019255:NADPH Oxidases / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases