Chemokine (C-C motif) ligand 20, a potential biomarker for Graves' disease, is regulated by osteopontin.
Chemokine (C-C motif) ligand 20, a potential biomarker for Graves' disease, is regulated by osteopontin.
复制标题
趋化因子（C-C 基序）配体 20 是格雷夫斯病的潜在生物标志物，受骨桥蛋白调节
DOI：
10.1371/journal.pone.0064277
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Li X;Qi Y;Ma X;Huang F;Guo H;Jiang X;Hong J;Lin D;Cui B;Ning G;Xu L;Wang S
Graves病（GD）是一种常见的累及甲状腺的自身免疫性疾病。促炎细胞因子和抗炎细胞因子的平衡改变在GD的发病机制中起重要作用。趋化因子（C-C基序）配体20（CCL20）对于白细胞介素-17（IL-17）信号激活和Th17细胞的有效化学引诱物是重要的。同时，骨桥蛋白（OPN）是一种广泛表达的多效性细胞因子，通过诱导Th1参与的反应，促进促炎细胞因子和趋化因子的产生，参与GD的发生，但OPN在调节CCL20和IL-17信号通路中的作用尚不清楚。本研究旨在探讨CCL20水平作为GD生物标志物的可能性，以及研究OPN在调节CCL20产生中的作用。招募了50名未经治疗的GD患者、15名甲状腺功能正常的GD患者、12名TRAb阴性的GD患者和35名健康对照供体。检测OPN、CCL20等临床GD诊断指标。使用抗体包被的磁珠从外周血单核细胞（PBMC）中分离CD4 + T细胞。采用酶联免疫吸附试验和定量聚合酶链反应检测CCL20的表达水平。我们发现血浆CCL20水平在GD患者中升高，而在甲状腺功能正常和TRAb阴性的GD患者中降低。此外，CCL20水平与GD临床诊断参数和血浆OPN水平相关。此外，我们证明重组OPN和来自未经治疗的GD患者的血浆增加了CD4 + T细胞中CCL20的表达，这可以被OPN抗体阻断。OPN通过β 3整合素受体、IL-17、NF-κ B和MAPK途径对CCL 20表达产生影响。这些结果表明，CCL20可能作为GD的生物标志物，并提示OPN在诱导CCL20表达中的可能作用。
Graves’ disease (GD) is a common autoimmune disease involving the thyroid gland. The altered balance of pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of GD. Chemokine (C-C motif) ligand 20 (CCL20) is important for interleukin-17 (IL-17) signal activation and a potent chemoattractant for Th17 cells. Meanwhile, Osteopontin (OPN), a broadly expressed pleiotropic cytokine, has been implicated in GD through inducing Th1-involved response to enhance the production of proinflammatory cytokines and chemokines, but little is known about the role of OPN in regulating CCL20 and IL-17 signaling. This study sought to explore the possibility of CCL20 level as a biomarker for GD, as well as investigate the role of OPN in regulating CCL20 production. Fifty untreated GD patients, fifteen euthyroid GD patients, twelve TRAb-negative GD patients and thirty-five healthy control donors were recruited. OPN, CCL20 and other clinical GD diagnosis parameters were measured. CD4+T cells were isolated from peripheral blood mononuclear cells (PBMCs) using antibody-coated magnetic beads. Enzyme-linked immune-sorbent assay and quantitative polymerase chain reaction were used to determine CCL20 expression level. We found that the plasma CCL20 level was enhanced in GD patients and decreased in euthyroid and TRAb-negative GD patients. In addition, CCL20 level correlated with GD clinical diagnostic parameters and plasma OPN level. Moreover, we demonstrated that recombinant OPN and plasma from untreated GD patients increased the expression of CCL20 in CD4+T cells, which could be blocked by OPN antibody. Furthermore, we found that the effect of OPN on CCL20 expression was mediated by β3 integrin receptor, IL-17, NF-κB and MAPK pathways. These results demonstrated that CCL20 might serve as a biomarker for GD and suggested the possible role of OPN in induction of CCL20 expression.
登录
查看更多内容
影响因子：
3.5
作者：
Guo, Ting;Huo, Ya'nan;Ning, Guang
通讯作者：
Ning, Guang
影响因子：
5.8
作者：
Antonelli, Alessandro;Ferrari, Silvia Martina;Fallahi, Poupak
通讯作者：
Fallahi, Poupak
影响因子：
4.8
作者：
Hirata, Tetsuya;Osuga, Yutaka;Taketani, Yuji
通讯作者：
Taketani, Yuji
影响因子：
4.4
作者：
Ghannam, Soufiane;Dejou, Cecile;Pene, Jerome
通讯作者：
Pene, Jerome
影响因子：
4.4
作者：
Mao, Chaoming;Wang, Shu;Zhang, Yanyun
通讯作者：
Zhang, Yanyun