Mouse monoclonal autoantibodies penetrate mouse macrophage cells and stimulate NF-κB activation and TNF-α release
Mouse monoclonal autoantibodies penetrate mouse macrophage cells and stimulate NF-κB activation and TNF-α release
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DOI：
10.1016/j.imlet.2009.04.005
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发表时间：
2009-06-04
影响因子：
4.4
通讯作者：
Jang, Young-Ju
中科院分区：
文献类型：
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作者：
Jang, Eun-Jung;Nahm, Dong-Ho;Jang, Young-Ju
系统性红斑狼疮（SLE）患者血清中存在抗双链DNA（dsDNA）自身抗体。然而，抗dsDNA抗体（Abs）参与SLE发病机制的机制尚未完全清楚。在这项研究中，我们研究了四种抗dsDNA小鼠单克隆自身抗体，它们在互补决定区共享带正电荷的氨基酸（包括精氨酸），以穿透RAW 264. 7巨噬细胞，激活NF-κ B和刺激TNF-α产生。所有四种抗体都渗透到巨噬细胞中并增加细胞外TNF-α的水平;两种抗体还激活NF-κ B。四种细胞穿透性抗dsDNA mAb中的两种诱导巨噬细胞中NF-κ B活化和TNF-α产生的事实表明，至少一些抗dsDNA的自身抗体可能通过穿透巨噬细胞和细胞核，随后通过结合NF-κ B基因并刺激其转录活性诱导促炎细胞因子TNF-α，从而在SLE的发病机制中发挥作用。(C)2009爱思唯尔有限公司版权所有。
Autoantibodies against double-stranded DNA (dsDNA) are found in the serum of systemic lupus erythematosus (SLE) patients. However, the mechanism by which anti-dsDNA antibodies (Abs) contribute to the pathogenesis of SLE is not yet fully understood. In this study, we investigated four anti-dsDNA mouse monoclonal autoantibodies that share positively charged amino acids (including arginines) in their complementarity determining regions for their ability to penetrate RAW264.7 macrophage cells, activate NF-kappa B and stimulate TNF-alpha production. All four antibodies penetrated into macrophage cells and increased the level of extracellular TNF-alpha; two also activated NF-kappa B. The fact that two of four cell-penetrating anti-dsDNA mAbs induced both NF-kappa B activation and TNF-alpha production in macrophages suggests that at least some autoantibodies against dsDNA may play a role in the pathogenesis of SLE by penetrating into macrophage cells and nuclei, and subsequently inducing the pro-inflammatory cytokine, TNF-alpha, by binding to the NF-kappa B gene and stimulating its transcriptional activity. (C) 2009 Elsevier B.V. All rights reserved.