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National Institute of Environmental Health Sciences

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Publication Detail

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

Authors: Ahmad, Nosheen; Chen, Li C; Gordon, Marion A; Laskin, Jeffrey D; Laskin, Debra L

Published In J Leukoc Biol, (2002 Jun)

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-gamma (IFN-gamma) 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 E2 (PGE2) 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-gamma. Inhibition of NOSII with aminoguanidine reduced COX-2 mRNA and protein expression as well as PGE2 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.

PubMed ID: 12050186 Exiting the NIEHS site

MeSH Terms: Acute Disease; Animals; Cells, Cultured; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors/pharmacology*; Dinoprostone/metabolism; Endotoxemia/enzymology; Endotoxemia/physiopathology*; Endotoxins/toxicity; Gene Expression Regulation, Enzymologic*/drug effects; Guanidines/pharmacology*; Isoenzymes/genetics*; Kupffer Cells/drug effects; Kupffer Cells/enzymology*; Lipopolysaccharides/pharmacology; Liver/enzymology; Nitric Oxide Synthase Type II; Nitric Oxide Synthase/genetics*; Nitric Oxide/physiology*; Prostaglandin-Endoperoxide Synthases/genetics*; Rats; Rats, Sprague-Dawley; Research Support, U.S. Gov't, P.H.S.; Reverse Transcriptase Polymerase Chain Reaction

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