Induction of hepatic ito cell nitric oxide production after acute endotoxemia

Abstract

Nitric oxide is a highly reactive mediator released in the liver by hepatocytes, Kupffer cells and endothelial cells during endotoxin-induced inflammation. In this study we determined whether Ito cells also produce nitric oxide after exposure to endotoxin. For induction of endotoxemia, rats were injected intravenously with Escherichia coli lipopolysaccharide (2.5 mg/kg). Ito cells were isolated from the animals 48 hr later by means of in situ perfusion of the liver with protease and collagenase followed by purification on an arabinogalactan gradient. Ito cells from untreated and endotoxemic rats were found to produce low levels of nitric oxide in response to interferon-gamma. In both cell types, this response depended on L-arginine and was blocked by NG-monomethyl-L-arginine, a specific nitric oxide synthase inhibitor. Cells from rats treated with endotoxin produced significantly more nitric oxide than did cells from untreated animals; this was due, at least in part, to increased expression of protein for an inducible form of nitric oxide synthase. These cells also responded to stimulation with lipopolysaccharide in vitro, as well as the combination of interferon-gamma and lipopolysaccharide, which was synergistic in stimulating nitric oxide production. Tumor necrosis factor-alpha and macrophage colony-stimulating factor were also found to stimulate nitric oxide production by Ito cells from endotoxemic rats. In addition, in these cells, tumor necrosis factor-alpha synergized with interferon-gamma in inducing nitric oxide production. The combination of interferon-gamma and lipopolysaccharide was also found to inhibit Ito cell DNA synthesis, as measured on the basis of [3H]-thymidine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of endotoxin-induced NO, IL-6, and TNF-α production in activated rat hepatic stellate cells: Role of p38 MAPK

“…[14][15][16] Endotoxin, in conjunction with interferon-␥, TNF-␣, and IL-1␤, also stimulates the synthesis of a multifunctional mediator NO in Kupffer cells 17 and hepatocytes. 18 Work from several laboratories, including ours, has demonstrated that endotoxin stimulates synthesis of NO via induction of inducible NO synthase (iNOS), 10,[19][20][21][22] and of TNF-␣ and IL-6 21,22 in both quiescent (normal liver) and activated (fibrotic liver) HSCs. TNF-␣ and IL-6, as well as increased NO (directly or via a potent free radical peroxinitrite), can exert a variety of effects on the hepatic system.…”

Nitric oxide donors stimulate bile flow and glutathione disulfide excretion independent of guanosine 3?,5?-cyclic monophosphate in the isolated perfused rat liver

“…26 As demon-in pathological conditions such as bacterial infections and sepsis that acutely increase NO systematically 1 and in the strated by this study, NO donors stimulated intrahepatic formation and biliary excretion of GSSG, whereas sinusoidal liver. [4][5][6] Chronic increases in NO production are seen in cirrhosis and portal hypertension. 54,55 Bacterial endotoxin, a poand canalicular GSH excretion remained unchanged.…”

“…[3][4][5][6] NO donors, such as sodium nitroprusside (SNP) has not been clearly defined. In the present study, we and S-nitroso-acetyl-penicillamine (SNAP), spontaneously examined the effects of NO on bile flow and biliary release NO in aqueous solution and have been used widely to HCO 0 3 and glutathione excretion in the isolated perfused study NO effects.…”

Effect of tenoxicam on rat liver tissue

“…On the other hand, nitric oxide (NO) is a compound with high oxidation capacity, which is produced from L-arginine amino acid via inducible NO synthase (iNOS) enzyme in hepatocytes and other connective tissue cells in the liver (10)(11)(12)(13)(14)(15)(16)(17). Therefore, it can be suggested that there is a positive correlation between liver damage and increase in NO levels.…”