Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway
Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway
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川崎病OX40-OX40L轴作为NFAT信号通路的上游调节因子
DOI：
10.1038/s41390-019-0312-0
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发表时间：
2019-05-01
影响因子：
3.6
通讯作者：
Ding, Yue-Yue
中科院分区：
文献类型：
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作者：
Lv, Yu-Wen;Chen, Ye;Ding, Yue-Yue
背景技术背景：我们研究了共刺激分子OX 40-OX 40 L在川崎（KD）急性期对活化T细胞核因子（NFAT）的上游调节作用。静脉注射免疫球蛋白（IVIG）前冠状动脉病变（KD-CAL），IVIG后KD-CAL，IVIG前无CAL的KD（KD-nCAL），IVIG后KD-nCAL，无名氏（Fou）发热，健康。分别在健康组和KD组中进行体外OX 40刺激和OX 40 L抑制试验。结果：KD-CAL组和KD-nCAL组IVIG前OX 40、OX 40 L、NFAT 1、NFAT 2 mRNA和蛋白表达水平均显著高于Fou组和Healthy组，IVIG后则显著低于Fou组和Healthy组。在KD中两者呈正相关。体外OX 40刺激实验显示，健康组外周血单个核细胞中NFAT 1和NFAT 2的mRNA和蛋白表达水平显著升高。结论：OX 40-OX 40 L在KD发病过程中参与了NFAT信号通路的上游调控。
BACKGROUND: We investigated a costimulatory molecule OX40-OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD).METHODS: One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively.RESULTS: The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group.CONCLUSION: OX40-OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.