The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis.
The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis.
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S100A8/A9 和 S100A12 在 MPO-ANCA 阳性血管炎患者中的潜在致病作用。
DOI：
10.1186/s12865-022-00513-4
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发表时间：
2022-09-10
期刊：
影响因子：
3
通讯作者：
Yan, Tie-Kun
中科院分区：
文献类型：
--
作者：
Bai, Xue;Xu, Peng-Cheng;Chen, Tong;Zhang, Hao-Miao;Wu, Si-Jing;Yang, Xia;Gao, Shan;Jia, Jun-Ya;Jiang, Jian-Qing;Yan, Tie-Kun
S100 A8/A9和S100 A12在抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）中的意义尚未阐明。本研究旨在探讨S100 A8/A9和S100 A12在髓过氧化物酶（MPO）-ANCA阳性血管炎患者中的潜在致病作用。检测了42例AAV患者血清和尿液中S100 A8/A9和S100 A12的浓度。研究了S100 A8/A9和S100 A12对MPO-ANCA激活的中性粒细胞的趋化性、凋亡、IL-1β释放、补体激活、呼吸爆发以及中性粒细胞胞外陷阱（NETs）形成的影响。活动性MPO-AAV患者血清和尿液中S100 A8/A9和S100 A12均显著升高（与非活动性AAV和健康对照组相比，p < 0.001），并与疾病严重程度相关。体外研究表明，S100 A8/A9和S100 A12激活p38 MAPK/NF-κB p65通路，增加MPO-ANCA激活的中性粒细胞的趋化指数（CI）和IL-1β的释放，延长其寿命，增强其补体激活能力。阻断TLR 4和TLR 4可抑制S100 A8/A9和S100 A12的作用。S100 A8/A9和S100 A12的所有上述作用均不依赖于ROS，因为S100 A8/A9和S100 A12均不增强MPO-ANCA激活的中性粒细胞的ROS形成和NETs形成。S100 A8/A9和S100 A12可作为评估疾病严重程度的标志物，也可能在MPO-AV发病机制中发挥作用。在线版本包含补充材料，可通过10.1186/s12865-022-00513-4获得。
The significance of S100A8/A9 and S100A12 in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. This study was dedicated to exploring the potential pathogenic roles of S100A8/A9 and S100A12 in patients with myeloperoxidase (MPO)-ANCA-positive vasculitis. Serum and urine concentrations of S100A8/A9 and S100A12 of forty-two AAV patients were evaluated. The influence of S100A8/A9 and S100A12 on the chemotaxis, the apoptosis, the release of IL-1β, the complement activation, the respiratory burst, as well as the neutrophil extracellular traps (NETs) formation of MPO-ANCA-activated neutrophils was investigated. The serum and urine S100A8/A9 and S100A12 of active MPO-AAV significantly increased (compared with inactive AAV and healthy controls, p < 0.001) and were correlated with the severity of the disease. In vitro study showed that S100A8/A9 and S100A12 activated the p38 MAPK/NF-κB p65 pathway, increased the chemotaxis index (CI) and the release of IL-1β, extended the life span, and enhanced the complement activation ability of MPO-ANCA-activated neutrophils. The Blockade of TLR4 and RAGE inhibited the effects of S100A8/A9 and S100A12. All above-mentioned effects of S100A8/A9 and S100A12 were ROS-independent because neither S100A8/A9 nor S100A12 enhanced the ROS formation and NETs formation of MPO-ANCA-activated neutrophils. S100A8/A9 and S100A12 serve as markers for assessing the disease severity, and they may also play a role in MPO-AAV pathogenesis. The online version contains supplementary material available at 10.1186/s12865-022-00513-4.
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影响因子：
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作者：
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作者：
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DOI：
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