Hepatocyte-derived interleukin-6 and tumor-necrosis factor alpha mediate the lipopolysaccharide-induced acute-phase response and nitric oxide release by cultured rat hepatocytes.
Hepatocyte-derived interleukin-6 and tumor-necrosis factor alpha mediate the lipopolysaccharide-induced acute-phase response and nitric oxide release by cultured rat hepatocytes.
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肝细胞源性白细胞介素 6 和肿瘤坏死因子 α 介导脂多糖诱导的急性期反应和培养大鼠肝细胞的一氧化氮释放。
DOI：
10.1111/j.1432-1033.1995.0349k.x
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Peter Maier
中科院分区：
文献类型：
--
作者：
B. Saad;K. Frei;F. A. Scholl;A. Fontana;Peter Maier
The regulation of acute-phase protein production and nitric oxide (NO) release in lipopolysaccharide-induced liver injury is thought to occur in response to monocytes/macrophages and Kupffer-cell-derived cytokines. In this study, we used primary cultured rat hepatocytes maintained as a differentiated phenotype to investigate the direct effects of endotoxin (lipopolysaccharide) on the production of the acute-phase proteins and on NO release. Lipopolysaccharide (10 micrograms/ml) increased the production of alpha 2-macroglobulin 2.5-fold compared to untreated cultures and decreased the production of albumin by 50%. The effect of lipopolysaccharide was mimicked by adding interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-alpha), cytokines being induced by treatment of hepatocytes with lipopolysaccharide. Maximal TNF-alpha (600 pg/ml) and IL-6 (1800 pg/ml) concentrations were observed 4 h and 6 h after lipopolysaccharide stimulation, respectively. The lipopolysaccharide-induced acute-phase protein response was blocked by anti-(IL-6) but not by anti-(TNF-alpha) IgG. The latter reduced the lipopolysaccharide-induced IL-6 production by 60%. Besides its effects on the acute-phase proteins, endotoxin caused a significant increase in NO production in cultured rat hepatocytes. Unlike anti-(IL-6) IgG, anti-(TNF-alpha) IgG reduced the lipopolysaccharide-induced NO production by 50% indicating that endotoxin-induced NO production is partially mediated by TNF-alpha but not by IL-6. Preculture with gadolinium chloride (GdCl3), an inhibitor of Kupffer cells, did not change the response of hepatocytes to lipopolysaccharide indicating that the observed findings are direct endotoxin effects on hepatocytes. The data demonstrate that by their production of TNF-alpha and IL-6 rat hepatocytes respond to lipopolysaccharide treatment with an IL-6 mediated acute-phase protein and a TNF-alpha-mediated NO production. These features have previously been attributed to monocytes/macrophages and Kupffer cells.
影响因子：
56.9
作者：
KARUPIAH, G;XIE, QW;MACMICKING, JD
通讯作者：
MACMICKING, JD
DOI：
10.1073/pnas.90.2.522
发表时间：
1993-01-15
影响因子：
11.1
作者：
GELLER, DA;NUSSLER, AK;BILLIAR, TR
通讯作者：
BILLIAR, TR