Inducible nitric oxide synthase modulates fibronectin production in the EA.hy926 cell line and cultured human umbilical vein endothelial cells

F. Pellegatta, A. Radaelli, E. Ferrero, E. Toninelli, M. J. Vidal, S. L. Chierchia, M. R. Zocchi

Research output: Contribution to journalArticle

Abstract

We wished to test the hypothesis of a connection existing between inducible nitric oxide (NO) synthesis and production of extracellular matrix proteins in endothelial cells (EC). We recently reported that the inducible-NO pathway contributes to cytokine-induced enhancement of tumor cell (TC) adhesion to cultured vascular endothelium, independent of changes in E-selectin expression on endothelial cells (EC). We now show that inducible NO-synthase is involved in enhancing fibronectin production by EC. Indeed, fibronectin synthesis and secretion increased both in the EA.hy926 EC line and in human umbilical vein EC (HUVEC) after prolonged exposure to tumor necrosis factor-α (TNF-α) or interferon-γ (IFN-γ). This effect was reversed by the reported inhibitor of NO synthase Nω-nitro-L-arginine methyl ester (L-NAME 10-5 M). The two cytokines exerted no additive effect, suggesting that they trigger a common metabolic pathway. NO production by cytokine-stimulated EC was dependent on the inducible NO-pathway, as demonstrated by studies of EC-dependent inhibition of platelet aggregation. This inhibition was also evident in calcium-free medium and was reversed by L-NAME and by two inhibitors of protein synthesis that are reported to block the inducible-NO synthase, such as dexamethasone (Dex 10-7 M) and cycloheximide (Chx 10-6 M). We conclude that modulation of the inducible NO-synthase may regulate matrix protein production by vascular endothelium during inflammation.

Original languageEnglish
Pages (from-to)1014-1019
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume24
Issue number6
Publication statusPublished - 1994

Keywords

  • cytokines
  • endothelial cells
  • fibronectin
  • nitric oxide

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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