Reactive oxygen species augment B-cell-activating factor expression
Reactive oxygen species augment B-cell-activating factor expression
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DOI：
10.1016/j.freeradbiomed.2006.02.007
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发表时间：
2006-06-15
影响因子：
7.4
通讯作者：
Yoon, Won-Kee
中科院分区：
文献类型：
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作者：
Moon, Eun-Yi;Lee, Jun-Hee;Yoon, Won-Kee
B细胞活化因子（BAFF）在成熟B细胞的生成和维持中起作用。脂多糖（LPS）激活Toll样受体4（TLR 4）依赖的信号转导并诱导ROS产生。在这里，我们研究了BAFF生产调节活性氧（ROS）。BAFF表达增加LPS刺激和血清剥夺诱导ROS的产生。BAFF的表达受到抑制的治疗与各种抗氧化剂，包括N-乙酰-L-半胱氨酸（NAC）。我们还研究了BAFF表达在体内使用过氧化物氧还蛋白II（PrxII）缺陷小鼠脾细胞。PrxII是抗氧化酶家族的成员，保护细胞免受氧化损伤。在缺乏PrxII的脾细胞中检测到内源性ROS的组成性产生。血清BAFF蛋白水平和脾细胞中BAFF转录本表达在PrxII（-/-）小鼠中显著高于野生型小鼠。较高的BAFF水平与较高的脾细胞和B220（+）细胞总数一致。根据I kappa B alpha降低的判断，结果得到了NF-kappa B激活的支持。在LPS刺激、血清剥夺和PrxII缺失的情况下，p65/RelA的降解和核转位增加。数据表明，TLR 4介导的BAFF表达被活性氧增加，并且被控制活性氧产生的PrxII抑制。(c)2006年爱思唯尔公司All rights reserved.
B-cell-activating factor (BAFF) plays a role in mature B-cell generation and maintenance. Lipopolysaccharide (LPS) activates toll-like receptor 4 (TLR4)-dependent signal transduction and induces ROS production. Here, we investigated BAFF production regulated by reactive oxygen species (ROS). BAFF expression was augmented by LPS stimulation and by serum deprivation that induced ROS production. BAFF expression was inhibited by treatment with various antioxidants including N-acetyl-L-cysteine (NAC). We also investigated BAFF expression in vivo using peroxiredoxin II (PrxII)-deficient mouse spleen cells. PrxII is a member of the antioxidant enzyme family that protects cells from oxidative damage. Constitutive production of endogenous ROS was detected in spleen cells lacking PrxII. Serum BAFF protein level and BAFF transcript expression in splenocytes were significantly higher in PrxII(-/-) mice than wildtype mice. A higher BAFF level is consistent with the higher total number of splenocytes and B220(+)cells. Results were supported by NF-kappa B activation as judged by reduced I kappa B alpha. degradation and increased nuclear translocation of p65/RelA with LPS stimulation, serum deprivation, and PrxII deletion. Data suggest that TLR4-mediated BAFF expression was increased by ROS and it was inhibited by PrxII controlling ROS production. (c) 2006 Elsevier Inc. All rights reserved.