Specific Increase in Joint Neutrophil Extracellular Traps and Its Relation to Interleukin 6 in Autoimmune Arthritis.
Specific Increase in Joint Neutrophil Extracellular Traps and Its Relation to Interleukin 6 in Autoimmune Arthritis.
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自身免疫性关节炎中关节中性粒细胞胞外陷阱的特异性增加及其与白细胞介素 6 的关系。
DOI：
10.3390/ijms22147633
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发表时间：
2021-07-16
影响因子：
5.6
通讯作者：
Matsumoto I
中科院分区：
文献类型：
--
作者：
Ohyama A;Osada A;Kawaguchi H;Kurata I;Nishiyama T;Iwai T;Ishigami A;Kondo Y;Tsuboi H;Sumida T;Matsumoto I
中性粒细胞及其细胞外陷阱在类风湿关节炎（RA）的发病中起重要作用，但其在关节中的具体机制尚不清楚，其调控机制也有待解决。在这里，我们探讨了中性粒细胞胞外陷阱（NET）在关节炎的实验模型，并进一步研究白细胞介素-6（IL-6）抑制中性粒细胞和NETosis的影响。在肽GPI诱导的关节炎（pGIA）的皮肤中，检测到瓜氨酸化蛋白以及免疫皮肤中的瓜氨酸化组蛋白表达，但这不是pGIA特异性的。pGIA关节中瓜氨酸化组蛋白表达对pGIA具有特异性，并与中性粒细胞弹性蛋白酶合并，提示NETosis。与骨髓中性粒细胞相比，关节中的中性粒细胞倾向于上调IL-6受体。在pGIA中施用小鼠抗IL-6受体抗体抑制关节炎，与关节中中性粒细胞浸润和NETosis的减少相关。在RA患者的血浆中，托珠单抗治疗后瓜氨酸化蛋白显著降低。我们的研究结果表明，IL-6增强中性粒细胞趋化性和NETosis在炎症关节，可能是瓜氨酸化蛋白的来源。
Neutrophils and their extracellular traps have been shown to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the detailed mechanisms in joints are still unclear, and their regulation remains to be solved. Here, we explored neutrophil extracellular trap (NET)osis in experimental models of arthritis and further investigated the effects of interleukin-6 (IL-6) inhibition in neutrophils and NETosis. In skins of peptide GPI-induced arthritis (pGIA), citrullinated protein was detected as well as citrullinated histone expression in immunized skin but this was not specific to pGIA. Citrullinated histone expression in pGIA joints was specific to pGIA and was merged with neutrophil elastase, suggesting NETosis. Neutrophils in joints tend to upregulate IL-6 receptors when compared with bone marrow neutrophils. Administration of mouse anti-IL-6 receptor antibodies in pGIA suppressed arthritis in association with a decrease in neutrophil infiltration and NETosis in joints. In the plasma of RA patients, citrullinated protein was significantly reduced after tocilizumab treatment. Our results suggest that IL-6 enhances neutrophil chemotaxis and NETosis in inflammatory joints and could be the source of citrullinated proteins.
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DOI：
10.1084/jem.20100239
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li P;Li M;Lindberg MR;Kennett MJ;Xiong N;Wang Y
通讯作者：
Wang Y
影响因子：
24.8
作者：
Carmona-Rivera, Carmelo;Carlucci, Philip M.;Kaplan, Mariana J.
通讯作者：
Kaplan, Mariana J.
影响因子：
2.2
作者：
Kawaguchi, Hoshimi;Matsumoto, Isao;Sumida, Takayuki
通讯作者：
Sumida, Takayuki
影响因子：
--
作者：
Nielen, MMJ;van Schaardenburg, D;Dijkmans, BAC
通讯作者：
Dijkmans, BAC
影响因子：
27.4
作者：
Boehler, Christoph;Radner, Helga;Aletaha, Daniel
通讯作者：
Aletaha, Daniel