Stimulation of endothelin-1 production by autoantibodies present in patients with scleroderma renal crisis

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2025-02-14 DOI:10.1016/j.clim.2025.110454

Pinchao Wang , Dashan Wu , Zexian Gong , Michael Adu-Gyamfi , Julian Kamhieh-Milz , Dennyson Leandro Mathias da Fonseca , Gülistan Sürücü , Muhammad I. Ashraf , Harald Heidecke , Dorota Sikorska , Otavio Cabral-Marques , Guido Moll , Gabriela Riemekasten , Janusz Witowski , Rusan Catar

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Abstract

Here, we investigate how autoantibodies against G protein-coupled receptors (GPCRs) on endothelial cells, which are present in patients with scleroderma renal crisis (SRC) impact on endothelin-1 (ET-1) production in human microvascular endothelial cells (HMECs). To this end, serum IgG fraction was isolated from SRC patients and applied to HMECs in culture. Compared to cells treated with either plain control medium or serum IgG from healthy individuals, exposure of HMECs to SRC-IgG resulted in a time- and concentration-dependent increase in ET-1 expression and release. This effect could be blocked by the protease activated receptor 1 (PAR1) inhibitor and mimicked by thrombin, the PAR1 activator. Transcription factor C-FOS/AP-1 and tissue factor (TF) were identified as mediators of these responses. Thus, it can be concluded that serum IgG fraction from SRC patients stimulates endothelial cells to produce ET-1, acting through PAR1 in cooperation with TF.

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硬皮病肾危重患者自身抗体对内皮素-1产生的刺激。

在这里，我们研究了存在于硬皮病肾危重症（SRC）患者内皮细胞上的G蛋白偶联受体（gpcr）自身抗体如何影响人微血管内皮细胞（HMECs）中内皮素-1 （ET-1）的产生。为此，从SRC患者中分离血清IgG，并将其应用于培养的HMECs。与普通对照培养基或健康人血清IgG处理的细胞相比，暴露于SRC-IgG的HMECs导致ET-1表达和释放的时间和浓度依赖性增加。这种作用可被蛋白酶激活受体1 （PAR1）抑制剂阻断，并可被PAR1激活剂凝血酶模拟。转录因子C-FOS/AP-1和组织因子（TF）被确定为这些反应的介质。由此可见，SRC患者血清IgG片段刺激内皮细胞产生ET-1，通过PAR1与TF协同作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.