Stephanz G B, Gwinner W, Cannon J K, Tisher C C, Nick H S
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville 32610, USA.
Exp Nephrol. 1996 May-Jun;4(3):151-8.
The response of the glomerular mesangial cell to reactive oxygen species (ROS) has been implicated in the pathogenesis of several forms of inflammatory renal disease. As a model of glomerular inflammation, we studied the effects of heat-aggregated immunoglobulin G (HAG), an experimental immune complex, and interleukin-1 (IL-1) on the expression of the antioxidant enzyme, manganese superoxide dismutase (MnSOD), in primary cultures of rat mesangial cells. Following exposure to either HAG or IL-1 beta, increased steady-state MnSOD mRNA levels were observed and an additive effect was seen following co-treatment with HAG and IL-1 beta. No change was observed in steady-state levels of copper/zinc superoxide dismutase mRNA with HAG or IL-1 beta exposure. RNA protein synthesis inhibitor experiments demonstrated that the HAG- and IL-1 beta-mediated increase in MnSOD mRNA was dependent on new transcription, but was independent of de novo protein synthesis. Our data on the induction of the MnSOD gene by immune complexes and IL-1 beta could indicate an important role for MnSOD in the cellular defense against ROS toxicity in glomerular inflammation.
肾小球系膜细胞对活性氧（ROS）的反应与多种炎症性肾脏疾病的发病机制有关。作为肾小球炎症的模型，我们研究了热聚集免疫球蛋白G（HAG，一种实验性免疫复合物）和白细胞介素-1（IL-1）对大鼠系膜细胞原代培养物中抗氧化酶锰超氧化物歧化酶（MnSOD）表达的影响。暴露于HAG或IL-1β后，观察到MnSOD mRNA稳态水平升高，且HAG与IL-1β联合处理后有相加效应。暴露于HAG或IL-1β时，铜/锌超氧化物歧化酶mRNA的稳态水平未观察到变化。RNA蛋白质合成抑制剂实验表明，HAG和IL-1β介导的MnSOD mRNA增加依赖于新的转录，但不依赖于从头合成蛋白质。我们关于免疫复合物和IL-1β诱导MnSOD基因的数据可能表明MnSOD在肾小球炎症中细胞防御ROS毒性方面起重要作用。
