Böhler T, Waiser J, Hepburn H, Gaedeke J, Lehmann C, Hambach P, Budde K, Neumayer H H
Department of Internal Medicine-Nephrology, Humboldt-University, Charité, Berlin, Germany.
Cytokine. 2000 Jul;12(7):986-91. doi: 10.1006/cyto.1999.0633.
Apoptosis of mesangial cells (MC) plays a role in glomerulonephritis (GN). In this study we investigated cytokine-induced apoptosis of cultured rat MC by morphological and biochemical features. TNF-alpha and IL-1alpha induced apoptosis in rat MC in a time- and concentration-dependent fashion. RT-PCR experiments revealed that MC express the TNF-receptor 1 (p60) gene constitutively. TNF-alpha as well as IL-1alpha stimulated the production of reactive oxygen species (ROS) and induced lipid peroxidation. Coincubation with catalase inhibited TNF-alpha and IL-1alpha induced apoptosis as well as lipid peroxidation. TNF-alpha, but not IL-1alpha increased the expression of c-jun. These results provide evidence that TNF-alpha and IL-1alpha induce apoptosis in rat MC with hydrogen peroxide and lipid peroxidation as second messengers. Increased c-jun expression may be a downstream intracellular signal of TNF-alpha-, but not IL-1alpha-induced apoptosis.
系膜细胞（MC）凋亡在肾小球肾炎（GN）中起作用。在本研究中，我们通过形态学和生化特征研究了细胞因子诱导的培养大鼠系膜细胞凋亡。肿瘤坏死因子-α（TNF-α）和白细胞介素-1α（IL-1α）以时间和浓度依赖性方式诱导大鼠系膜细胞凋亡。逆转录-聚合酶链反应（RT-PCR）实验显示系膜细胞组成性表达肿瘤坏死因子受体1（p60）基因。TNF-α以及IL-1α刺激活性氧（ROS）产生并诱导脂质过氧化。与过氧化氢酶共同孵育可抑制TNF-α和IL-1α诱导的凋亡以及脂质过氧化。TNF-α而非IL-1α增加c-jun的表达。这些结果证明TNF-α和IL-1α以过氧化氢和脂质过氧化作为第二信使诱导大鼠系膜细胞凋亡。c-jun表达增加可能是TNF-α而非IL-1α诱导凋亡的下游细胞内信号。
