Protein disulfide isomerase suppresses the transcriptional activity of NF-kB
Protein disulfide isomerase suppresses the transcriptional activity of NF-kB
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DOI：
10.1016/j.bbrc.2004.04.002
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发表时间：
2004-05-21
影响因子：
3.1
通讯作者：
Waga, I
中科院分区：
文献类型：
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作者：
Higuchi, T;Watanabe, Y;Waga, I
我们在此报告，NF-kappaB 的转录活性受到蛋白质二硫键异构酶 (PDI) 的负向调节。 RAW 264.7 细胞中 PDI 的过度表达强烈抑制 LPS 诱导的炎症细胞因子的产生以及 NF-κB 依赖性荧光素酶活性。 PDI 抑制剂杆菌肽可逆转 NF-κB 的这种负调节。有趣的是，在 LPS 刺激后，表达 PDI 的细胞中 NF-kappaB/DNA 复合物的形成和 NF-kappaB 亚基的磷酸化是完整的。此外，PDI和另一种氧化还原调节剂硫氧还蛋白（TRX）对NF-κB依赖性基因表达具有相反的作用：TRX对NF-κB通路的激活被PDI的表达以剂量依赖性方式抑制。最后，抗炎细胞因子 IL-10 诱导 PDI 表达，杆菌肽可减少 IL-10 介导的 LPS 诱导的 IL-6 表达抑制。这些发现清楚地表明 PDI 是 NF-kappaB 的负调节因子，并且可能在该信号通路中作用于 IL-10 的下游。 (C) 2004 Elsevier Inc. 保留所有权利。
We report here that the transcriptional activity of NF-kappaB is negatively regulated by protein disulfide isomerase (PDI). Overexpression of PDI in RAW 264.7 cells strongly suppressed the LPS-induced production of inflammatory cytokines as well as NF-kappaBdependent luciferase activity. This negative regulation of NF-kappaB was reversed by bacitracin, a PDI inhibitor. Interestingly, NF-kappaB/ DNA complex formation and phosphorylation of NF-kappaB subunits was intact in PDI-expressing cells following stimulation with LPS. In addition, PDI and another redox regulator, thioredoxin (TRX), had opposite effects on NF-kappaB-dependent gene expression: activation of the NF-kappaB pathway by TRX was suppressed by expression of PDI in a dose-dependent manner. Finally, PDI expression was induced by the anti-inflammatory cytokine IL-10, and IL-10-mediated inhibition of LPS-induced IL-6 expression was reduced by bacitracin. These findings clearly demonstrate that PDI is a negative regulator of NF-kappaB, and may act downstream of IL-10 in this signaling pathway. (C) 2004 Elsevier Inc. All rights reserved.