Interleukin 1 β markedly stimulates nitric oxide formation in the absence of other cytokines or lipopolysaccharide in primary cultured rat hepatocytes but not in Kupffer cells

✍ Scribed by H Kitade; K Sakitani; K Inoue; Y Masu; N Kawada; Y Hiramatsu; Y Kamiyama; T Okumura; S Ito

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 500 KB
• Volume: 23
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510230421

✦ Synopsis

absence of other cytokines or LPS. (HEPATOLOGY To investigate whether a single inflammatory cyto-1996;23:797-802.) kine could stimulate nitric oxide formation in the absence of other cytokines or lipopolysaccharide (LPS), NO was measured by the redox chemiluminescence Nitric oxide plays an important role in many physiomethod in primary cultured rat hepatocytes and in rat logical functions, such as the regulation of vascular Kupffer cells. Interleukin (IL) 1b, but neither IL-6, tumor tone, neurotransmission, and the mediation of immune necrosis factor a (TNF-a), interferon gamma (IFN-g), nor

responses. 1 In vivo, NO has been reported to have pro-LPS stimulated NO formation in a dose-dependent manner and induced half-maximal effects at 30 pmol/L. Maxi-tective effects during the inflammation and endotoxemal stimulation was achieved at 12 to 16 hours after the mia associated with hepatic injury. 2 In contrast, NO addition of 1 nmol/L of IL-1b, and was 50-to 60-fold above has also been reported to induce hepatic mitochondrial basal levels in rat hepatocytes. The combined effect of dysfunction both in perfused liver and isolated hepatothese cytokines with LPS or IFN-g on NO formation was cytes. 3 Interleukin (IL)1b, tumor necrosis factor a also examined. Neither LPS nor IFN-g affected the IL-(TNF-a), and endotoxins have all been shown to stimu-1b-induced NO formation. TNF-a, however, stimulated late NO formation in hepatocytes and in Kupffer cells IL-1b-induced NO formation, while IL-6 inhibited it, alcultured from chronically endotoxemic rats 4 or turpenthough independently these cytokines had no effect on tine-injected rats. 5 NO is synthesized from L-arginine NO formation. None of the cytokines tested stimulated by NO synthases (NOS). These enzymes can be classi-NO formation in cultured rat Kupffer cells. In hepatocytes, the NO formation induced by IL-1b was blocked by fied into at least two distinct groups. Constitutive NOS both the NO synthase (NOS) inhibitor N G -monomethyl-Lis present in endothelium 6 and in brain. 7 Inducible arginine (L-NMMA) and by IL-1 receptor antagonist (IL-NOS (iNOS) is present in negligible quantities under 1ra). Furthermore, IL-1b markedly increased NOS activphysiological conditions, but is highly expressed in reity, and this increase in activity was accompanied by sponse to stimuli such as endotoxins and cytokines, the expression of inducible NOS (iNOS) messenger RNA in a variety of cells including vascular smooth muscle (mRNA). This study clearly demonstrated that IL-1b cells, 8,9 macrophages, 10 and liver cells. [11][12][13] Within the markedly stimulates NO formation in hepatocytes, in the liver, however, it is not clear whether the Kupffer cells or the hepatocytes are the primary producers of NO. In order to elucidate the mechanism by which cytokines induce NO formation within the liver, a sensitive Abbreviations: IL, interleukin; TNF-a, tumor necrosis factor a; NOS, nitric oxide synthase; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; chemiluminescence system was employed for the mea-IL-1ra, IL-1 receptor antagonist; L-NMMA, N G -monomethyl-L-arginine; IFN-surement of NO in the present study. Furthermore, g, interferon gamma; mRNA, messenger RNA; PCR, polymerase chain reacthe question of whether a single inflammatory cytokine tion; RT-PCR, reverse-transcription polymerase chain reaction.