NF-κB Is Required for Cytokine-Induced Manganese Superoxide Dismutase Expression in Insulin-Producing Cells1.
NF-κB Is Required for Cytokine-Induced Manganese Superoxide Dismutase Expression in Insulin-Producing Cells1.
复制标题
细胞因子诱导的胰岛素生产细胞中锰超氧化物歧化酶表达需要 NF-κB1。
作者：
M. Darville;Y. Ho;D. Eizirik
活性氧在1型糖尿病炎症细胞因子对胰岛β细胞的细胞毒性作用中起重要作用。抗氧化酶锰超氧化物歧化酶（MnSOD）是细胞防御这些有害自由基的一部分。MnSOD基因的表达是由细胞因子诱导的胰岛素分泌细胞，但MnSOD在这些细胞中的表达的转录调控还没有得到很好的理解。在这份报告中，我们研究了转录调控细胞因子的大鼠MnSOD基因在胰岛素分泌细胞。通过瞬时转染启动子荧光素酶报告构建体，我们确定了两个白细胞介素（IL）-1 β反应元件，赋予每个添加剂3倍IL-1 β诱导的转录活性。第一个位于启动子区，而第二个位于MnSOD基因的第二个内含子中。有趣的是，内含子元件是干扰素-γ诱导的增强所必需的。定点突变和带移分析表明，在每个区域的NF-κ B结合位点是必要的，但不是足够的，IL-1 β的转录诱导。我们的研究结果表明，NF-κ B可能与CCAAT/增强子结合蛋白因子的启动子区域和八聚体和Ets因子的内含子区域。
Reactive oxygen species play an important role in the cytotoxic effect of inflammatory cytokines on pancreatic beta-cells in type 1 diabetes mellitus. The antioxidant enzyme manganese superoxide dismutase (MnSOD) is part of the cellular defenses against these deleterious radicals. MnSOD gene expression is induced by cytokines in insulin-producing cells, but the transcriptional regulation of MnSOD expression in these cells is not well understood. In this report, we investigated the transcriptional regulation by cytokines of the rat MnSOD gene in insulin-producing cells. By transient transfections with promoter-luciferase reporter constructs, we identified two interleukin (IL)-1beta-responsive elements, conferring each an additive 3-fold IL-1beta-induced transcriptional activity. The first is located in the promoter region, whereas the second is located in the second intron of the MnSOD gene. Interestingly, the intronic element is required for interferon-gamma-induced potentiation. Site-directed mutagenesis and band-shift assays showed that an NF-kappaB binding site in each region is necessary, but not sufficient, for transcriptional induction by IL-1beta. Our results suggest that NF-kappaB may cooperate with CCAAT/enhancer-binding protein factors in the promoter region and with octamer and Ets factors in the intronic region.
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DOI：
10.1073/pnas.90.10.4679
发表时间：
1993-05-15
影响因子：
11.1
作者：
VALLEJO, M;RON, D;HABENER, JF
通讯作者：
HABENER, JF
影响因子：
15.9
作者：
Hohmeier, HE;Thigpen, A;Newgard, CB
通讯作者：
Newgard, CB
一氧化氮、超氧化物和过氧亚硝酸盐：好的、坏的和丑陋的。
DOI：
10.1152/ajpcell.1996.271.5.c1424
发表时间：
1996
期刊：
The American journal of physiology
影响因子：
--
作者：
Beckman,JS;Koppenol,WH
通讯作者：
Koppenol,WH
影响因子：
2.9
作者：
Chung, DJ;Wright, AE;Clerch, LB
通讯作者：
Clerch, LB