Inhibition of LPS-induced nitric oxide and TNF-α production by α-lipoic acid in rat Kupffer cells and in RAW 264.7 murine macrophages

被引:81
作者
Kiemer, AK [1 ]
Ller, CM [1 ]
Vollmar, AM [1 ]
机构
[1] Univ Munich, Dept Pharm, Ctr Drug Res, D-81377 Munich, Germany
关键词
activator protein-1; antioxidant; inflammation; liver; nuclear factor-kappa B; transcription factors;
D O I
10.1046/j.1440-1711.2002.01124.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The activation of Kupffer cells represents a central mechanism of inflammatory liver injury involving the production of two important inflammatory mediators, nitric oxide and TNF-alpha. The aim of this study was to investigate the effect of the hepatoprotective compound alpha-lipoic acid (thioctic acid) on the production of nitric oxide and TNF-alpha in isolated rat Kupffer cells and RAW 264.7 macrophages. Isolated rat Kupffer cells or RAW 264.7 were either untreated, treated with alpha-lipoic acid (500 mug/mL), or activated with 1 mug/mL of lipopolysaccharide in the presence or absence of alpha-lipoic acid (0.2-500 mug/mL). After 20 h the accumulation of nitrite was measured by the Griess assay. Tumour necrosis factor-alpha secretion was quantified after 4 h by L929 bioassay. Cell viability was determined by mitochondrial reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) DNA binding activity by gelshift assays. Treatment of Kupffer cells and RAW 264.7 with alpha-lipoic acid alone had no effect on basal nitric oxide production. However, alpha-lipoic acid significantly inhibited lipopolysaccharide-induced nitrite accumulation. alpha-Lipoic acid did not alter basal TNF-alpha secretion in Kupffer cells, whereas it significantly inhibited lipopolysaccharide-induced TNF-alpha production. alpha-Lipoic acid attenuated the activation of nuclear factor-kappaB and AP-1, two transcription factors pivotal in induction of inducible nitric oxide synthase and TNF-alpha. alpha-Lipoic acid significantly inhibits lipopolysaccharide-induced macrophage production of nitric oxide and TNF-alpha via an attenuated activation of NF-kappaB and activator protein-1. The reduced production of nitric oxide and TNF-alpha in Kupffer cells may be involved in the hepatoprotective action conveyed by alpha-lipoic acid.
引用
收藏
页码:550 / 557
页数:8
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