IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway.
IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway.
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IL-37b通过IL-1R8通路减轻川崎病内皮细胞凋亡和炎症
DOI：
10.1038/s41419-021-03852-z
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发表时间：
2021-06-03
影响因子：
9
通讯作者：
Chu M
中科院分区：
文献类型：
--
作者：
Jia C;Zhuge Y;Zhang S;Ni C;Wang L;Wu R;Niu C;Wen Z;Rong X;Qiu H;Chu M
川崎（KD）是一种急性血管炎的儿童人群，可能发展冠状动脉瘤，如果不治疗。它被认为是发达国家儿童获得性心脏病的主要原因。白细胞介素（IL）-37作为IL-1家族成员之一，是天然的炎症抑制剂，所述炎症是由先天免疫和获得性免疫激活引起的。然而，IL-37在KD中的详细作用在很大程度上尚不清楚。KD患者血清IL-37水平较健康对照组明显降低。QRT-PCR和western blot分析显示，IL-37变体IL-37 b在暴露于KD血清处理的THP 1细胞的人脐静脉内皮细胞（HUVECs）中的表达水平显著下调。因此，我们研究了IL-37 b在KD背景下的作用，并假设IL-37 b可能在KD患者中具有强大的保护作用。我们首次观察并证实了白念珠菌细胞壁提取物（CAWS）诱导的KD小鼠模型中IL-37 b的保护作用。体外实验表明，IL-37 B通过抑制ERK和NFκB B活化，通过IL-1 R8受体减轻内皮细胞凋亡和炎症，这也在KD小鼠模型中得到重现。总之，我们的研究结果表明，IL-37 b在KD冠状动脉内皮损伤中发挥有效的保护作用，为IL-37 b是治疗KD的潜在候选药物提供了新的证据。
Kawasaki disease (KD) is an acute vasculitis of pediatric populations that may develop coronary artery aneurysms if untreated. It has been regarded as the principal cause of acquired heart disease in children of the developed countries. Interleukin (IL)-37, as one of the IL-1 family members, is a natural suppressor of inflammation that is caused by activation of innate and adaptive immunity. However, detailed roles of IL-37 in KD are largely unclear. Sera from patients with KD displayed that IL-37 level was significantly decreased compared with healthy controls (HCs). QRT-PCR and western blot analyses showed that the expression level of IL-37 variant, IL-37b, was remarkably downregulated in human umbilical vein endothelial cells (HUVECs) exposed to KD sera-treated THP1 cells. Therefore, we researched the role of IL-37b in the context of KD and hypothesized that IL-37b may have a powerful protective effect in KD patients. We first observed and substantiated the protective role of IL-37b in a mouse model of KD induced byCandida albicanscell wall extracts (CAWS). In vitro experiments demonstrated that IL-37b alleviated endothelial cell apoptosis and inflammation via IL-1R8 receptor by inhibiting ERK and NFκB activation, which were also recapitulated in the KD mouse model. Together, our findings suggest that IL-37b play an effective protective role in coronary endothelial damage in KD, providing new evidence that IL-37b is a potential candidate drug to treat KD.
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