Induction of cyclo-oxygenase-2 in human endothelial cells by SIN-1 in the absence of prostaglandin production

Sonia Eligini, Aïda Habib, Marilyne Lebret, Christophe Créminon, Sylviane Lévy-Toledano, Jacques Maclouf

Research output: Contribution to journalArticle

Abstract

1. Nitric oxide (NO) regulates cyclo-oxygenase (COX) activity in various cell systems and reports conflict in regard to its stimulatory versus inhibitory role. Incubation of human umbilical vein endothelial cells (HUVEC) with SIN-1 (3-morpholinosydnonimine), a donor of NO, resulted in a rapid and dose-dependent increase in the expression of COX-2 as analysed by Western and Northern blotting. 2. Incubation of HUVEC with SIN-1 and interleukine (IL)-1α resulted in increased induction of COX-2 compared with IL-1α alone and corresponded to an additive effect. The COX-2 induction was dependent on a de novo synthesis since cycloheximide, an inhibitor of protein synthesis, blocked the enzyme expression. The increase in COX-2 expression was not accompanied by a corresponding change in prostaglandin (PG) production. However, the COX activity was partially recovered when immunoprecipitated COX-2 was incubated with arachidonic acid and haematin. 3. Peroxynitrite, a highly reactive nitrogen molecule derived from the interaction of NO and superoxide anion, significantly increased COX-2 expression. Under these conditions and within the limit of detection of the antibody, selective antibody for nitrotyrosine failed to detect nitrated COX-2 in immunoprecipitated COX-2 when cells where incubated with SIN-1 or SIN-1 + IL-1α. 4. Ro 31-8220, a specific inhibitor of protein kinase (PK) C, blocked the induction of COX-2. Also, SB203580, the selective inhibitor of p38 MAP kinase, strongly blocked the induction of COX-2 by SIN-1 in the presence or absence of IL-1α, whereas the MEK-1 inhibitor, PD 98059, affected it to a lesser extent. These data demonstrate that SIN-1 induces COX-2 in HUVEC in the absence of PG formation and suggest a complex regulation of COX-2 expression and PG formation by NO in endothelial cells.

Original languageEnglish
Pages (from-to)1163-1171
Number of pages9
JournalBritish Journal of Pharmacology
Volume133
Issue number7
Publication statusPublished - 2001

Keywords

  • COX-2
  • Endothelial cells
  • MAP kinases
  • Nitric oxide (NO)
  • Prostacyclin
  • SIN-1

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Eligini, S., Habib, A., Lebret, M., Créminon, C., Lévy-Toledano, S., & Maclouf, J. (2001). Induction of cyclo-oxygenase-2 in human endothelial cells by SIN-1 in the absence of prostaglandin production. British Journal of Pharmacology, 133(7), 1163-1171.