川崎病 OX40-OX40L 轴作为 NFAT 信号通路的上游调节剂。

Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway.

机构信息

Cardiology Department, Children's Hospital of Soochow University, 215025, Suzhou, Jiangsu Province, China.

Institute of Pediatric Research, Children's Hospital of Soochow University, 215025, Suzhou, Jiangsu Province, China.

出版信息

Pediatr Res. 2019 May;85(6):835-840. doi: 10.1038/s41390-019-0312-0. Epub 2019 Jan 25.

DOI:10.1038/s41390-019-0312-0

PMID:30723312

Abstract

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.

摘要

背景

我们研究了一种共刺激分子 OX40-OX40L，它作为上游调节剂，在川崎病（KD）的急性期调节活化 T 细胞核因子（NFAT）。

方法

收集了 101 个样本，分为 6 组：静脉注射免疫球蛋白（IVIG）前冠状动脉病变（KD-CAL）、IVIG 后 KD-CAL、IVIG 前无冠状动脉病变（KD-nCAL）、IVIG 后 KD-nCAL、发热原因不明（Fou）和健康对照组。分别对健康组和 KD 组进行体外 OX40 刺激和 OX40L 抑制试验。采用定量逆转录 PCR 和免疫印迹法分别检测 OX40、OX40L、NFAT1 和 NFAT2 的信使 RNA（mRNA）和蛋白表达水平。

结果

与 Fou 和健康对照组相比，IVIG 前 KD-CAL 和 KD-nCAL 组的 NFAT1、NFAT2、OX40 和 OX40L 的 mRNA 和蛋白表达水平显著升高，IVIG 后降低。KD 组之间存在正相关。体外 OX40 刺激试验显示，健康组外周血单个核细胞中 NFAT1 和 NFAT2 的 mRNA 和蛋白表达水平显著升高。同时，OX40L 抑制试验显示 KD 组 NFAT1 和 NFAT2 的表达水平明显降低。