Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia

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Abstract

Eicosanoids generated via cyclooxygenase-2 (COX-2) and nitric oxide produced from inducible nitric oxide synthase (NOSII) have been implicated in endotoxin-induced tissue injury. In the present studies, we characterized COX-2 and NOSII activity in rat hepatic macrophages and their interaction during acute endotoxemia. Kupffer cells from control animals were found to constitutively express COX-2 and NOSII mRNA and protein. Whereas treatment of the cells with lipopolysaccharide (LPS) and/or interferon-γ (IFN-γ) had no major effect on COX-2, NOSII expression increased. Induction of acute endotoxemia resulted in a rapid and transient increase in constitutive COX-2 expression and prostaglandin E 2 (PGE 2) production by liver macrophages as well as NOSII expression and nitric oxide release. Cells from endotoxin-treated rats were also sensitized to generate more nitric oxide and express increased NOSII in response to LPS and IFN-γ. Inhibition of NOSII with aminoguanidine reduced COX-2 mRNA and protein expression as well as PGE 2 production by activated macrophages from endotoxemic, but not control animals. In contrast, SC236, a specific COX-2 inhibitor, had no effect on NOSII mRNA or protein levels or on nitric oxide production by hepatic macrophages, even after endotoxin administration. These data suggest that activation of COX-2 may be important in the pathophysiological response of hepatic macrophages to endotoxin. Moreover, nitric oxide is involved in regulating COX-2 in activated liver macrophages during acute endotoxemia.

Original languageEnglish (US)
Pages (from-to)1005-1011
Number of pages7
JournalJournal of Leukocyte Biology
Volume71
Issue number6
StatePublished - Jun 1 2002

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Keywords

  • Kupffer cells
  • Liver
  • NOSII
  • PGE

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