The Impact of Redox State on Regulation of the High-Affinity IgE Receptor Expression
The Impact of Redox State on Regulation of the High-Affinity IgE Receptor Expression
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氧化还原状态对高亲和力 IgE 受体表达调节的影响
DOI：
10.1007/978-90-481-3892-0_42
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
H. Tachibana
中科院分区：
文献类型：
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作者：
Y. Fujimura;H. Higo;S. Yano;Koji Yamada;H. Tachibana
高亲和力IgE受体（Fc IgE RI）表达于肥大细胞和嗜碱性粒细胞的细胞表面，并在IgE介导的炎症反应中发挥核心作用。15-脱氧-Δ 12，14-前列腺素J2（15 d-PGJ 2）是过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor γ，PPARγ）的天然配体。然而，其内在机制仍不清楚。在这里，我们研究了PPARγ是否参与15 d-PGJ 2的作用。RNA干扰介导的PPARγ表达下调并不影响15 d-PGJ 2的作用，这表明15 d-PGJ 2的抑制作用可能是由于PPARγ非依赖性机制所致。一般认为，15 d-PGJ 2是一种能引起细胞内氧化应激和氧化还原改变的强亲电体。在本研究中，观察到15 d-PGJ 2处理的KU 812细胞中活性氧（ROS）水平增加，并且通过加入N-乙酰半胱氨酸或过氧化氢酶来消除。15 d-PGJ_2对Fc γ RI表达的抑制作用也可被过氧化氢酶抑制。以前，我们已经报道了细胞外信号调节激酶1/2（ERK 1/2）磷酸化的减少参与了Fc γ RI表达的下调。15 d-PGJ 2可抑制KU 812细胞ERK 1/2的磷酸化，而过氧化氢酶可抑制这种作用。总之，这些结果表明，15 d-PGJ 2诱导的ROS如过氧化氢的上调可能有助于抑制ERK 1/2磷酸化，随后抑制Fc ERK RI表达。这是第一个报告表明参与的氧化还原状态的Fc γ RI表达的调节。
The high-affinity IgE receptor (FcɛRI) is expressed on the cell surface of mast cells and basophils, and plays a central role in IgE-mediated inflammatory reactions. We have reported that 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2), a natural ligand for peroxisome proliferator-activated receptor γ (PPARγ), was able to suppress the FcɛRI expression of the human basophilic KU812 cells. However, the underlying mechanism still remained unclear. Here we examined whether PPARγ is involved in the action of 15d-PGJ2. RNA interference-mediated downregulation of PPARγ expression did not affect the action of 15d-PGJ2, suggesting that the suppressive effect of 15d-PGJ2may be due to the PPARγ-independent mechanism. Generally, 15d-PGJ2is known to be a potent electrophile that causes intracellular oxidative stress and redox alteration. In the present study, the increased levels of reactive oxygen species (ROS) were observed in KU812 cells treated with 15d-PGJ2, and which was abolished by the addition ofN-acetylcysteine or catalase. Moreover, the suppressive effect of 15d-PGJ2on FcɛRI expression was also inhibited by catalase. Previously, we have reported that the reduction of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was involved in the downregulation of FcɛRI expression. 15d-PGJ2diminished the phosphorylation of ERK1/2 in KU812 cells, and this effect was prevented upon treatment with catalase. Taken together, these results suggest that 15d-PGJ2-induced upregulation of ROS such as hydrogen peroxide may contribute to the inhibition of ERK1/2 phosphorylation, followed by the suppression of FcɛRI expression. This is the first report showing the involvement of redox state in the regulation of FcɛRI expression.