title: The endothelium and cytokine secretion: the role of peroxidases as immunoregulators.
abstract: The endothelium is frequently exposed to many proinflammatory mediators. The present study was done to determine the effects of human recombinant myeloperoxidase (MPO) and porcine eosinophil peroxidase (EPO) on certain endothelial cell (HUVEC) functions. The following areas were evaluated: (1) production of reactive oxygen intermediates (ROI), (2) cytokine secretion, and (3) regulation of mRNA cytokine transcripts. Both MPO and EPO induced the production of ROI, but an enzymatically inactive form of MPO (iMPO) was the most effective. Enzymatically inactive MPO, but not MPO, induced the secretion of interleukins 6 and 8 and granulocyte-monocyte colony-stimulating factor. A ribonuclease protection assay indicated that both iMPO and MPO upregulated mRNA cytokine transcripts; however, the former was markedly more effective. The simultaneous addition of EPO and iMPO resulted in a decrease in cytokine-specific mRNA. These data indicate a major role for peroxidases in the regulation of inflammation.
authors.affiliation: Department of Biological Sciences, Texas Tech University, Lubbock, Texas, 79409, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Lefkowitz
authors.forename: E
authors.initials: E
authors.lastname: Roberts
authors.forename: K
authors.initials: K
authors.lastname: Grattendick
authors.forename: C
authors.initials: C
authors.lastname: Schwab
authors.forename: R
authors.initials: R
authors.lastname: Stuart
authors.forename: J
authors.initials: J
authors.lastname: Lincoln
authors.forename: R C
authors.initials: RC
authors.lastname: Allen
authors.forename: N
authors.initials: N
authors.lastname: Moguilevsky
authors.forename: A
authors.initials: A
authors.lastname: Bollen
authors.forename: S S
authors.initials: SS
authors.lastname: Lefkowitz
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology; D047209:Eosinophil Peroxidase; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009195:Peroxidase / Q000494:pharmacology; D010544:Peroxidases / Q000494:pharmacology*; D012333:RNA, Messenger / Q000302:isolation & purification; D017382:Reactive Oxygen Species; D016897:Respiratory Burst; D013552:Swine; D014471:Umbilical Veins; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D009195:Peroxidase