Gwinner W, Tisher C C, Nick H S
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, USA.
Kidney Int. 1995 Aug;48(2):354-62. doi: 10.1038/ki.1995.303.
Reactive oxygen species have been implicated as mediators of tissue injury in glomerular inflammation. The expression of the antioxidant enzyme, manganese superoxide dismutase (MnSOD), was examined in primary cultures of rat glomerular epithelial cells (GEC) in response to inflammatory mediators. The results demonstrate that GEC respond to interleukin-1 (IL-1) and bacterial lipopolysaccharride (LPS) with an increase in MnSOD steady-state mRNA levels. The IL-1 alpha-mediated induction of MnSOD mRNA levels was both time- and dose-dependent. Maximal levels approximately 40-fold above controls, were observed at 12 hours with 2 ng/ml of IL-1 alpha. MnSOD protein levels were also markedly elevated by IL-1 alpha. The induction of MnSOD mRNA by IL-1 alpha required de novo transcription as well as some degree of protein synthesis. To elucidate the potential intracellular signal that mediates IL-1 alpha-dependent MnSOD expression, three classical signaling pathways were examined. We found no evidence that MnSOD induction by IL-1 alpha is mediated by either the cyclooxygenase or lipoxygenase pathway or via activation of protein kinase C. Based on the presence of IL-1 alpha in several forms of glomerular inflammation, the observed increase in MnSOD expression by this immunoregulatory cytokine must have an important role in the antioxidant defense of glomerular epithelial cells.
活性氧已被认为是肾小球炎症中组织损伤的介质。在大鼠肾小球上皮细胞（GEC）原代培养物中，检测抗氧化酶锰超氧化物歧化酶（MnSOD）对炎症介质的反应性表达。结果表明，GEC对白细胞介素-1（IL-1）和细菌脂多糖（LPS）的反应是MnSOD稳态mRNA水平升高。IL-1α介导的MnSOD mRNA水平诱导具有时间和剂量依赖性。在2 ng/ml IL-1α作用12小时时，观察到最大水平比对照高约40倍。IL-1α也显著提高了MnSOD蛋白水平。IL-1α诱导MnSOD mRNA需要从头转录以及一定程度的蛋白质合成。为了阐明介导IL-1α依赖性MnSOD表达的潜在细胞内信号，研究了三种经典信号通路。我们没有发现证据表明IL-1α诱导MnSOD是由环氧化酶或脂氧化酶途径或通过蛋白激酶C的激活介导的。基于几种形式的肾小球炎症中存在IL-1α，这种免疫调节细胞因子导致的MnSOD表达增加必定在肾小球上皮细胞的抗氧化防御中起重要作用。
