Increased chemokine (C-C motif) ligand 21 expression and its correlation with osteopontin in Graves' disease
Increased chemokine (C-C motif) ligand 21 expression and its correlation with osteopontin in Graves' disease
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DOI：
10.1007/s12020-015-0552-7
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发表时间：
2015-09-01
期刊：
影响因子：
3.7
通讯作者：
Wang, Shu
中科院分区：
文献类型：
--
作者：
Qi, Yicheng;Li, Xiaoli;Wang, Shu
Graves病(GD)是一种慢性自身免疫过程，其特征是产生自身抗体，推测是由于淋巴细胞在甲状腺中的渗透所致。趋化因子(C-C基序)配体21(CCL21)对CC-趋化因子受体7(CCR7)表达细胞的循环起重要作用。同时，骨桥蛋白(OPN)通过核因子-kappaB和MAPK信号通路促进GD患者促炎细胞因子和趋化因子的产生。尽管CCL21已被报道在多种自身免疫性疾病中起重要作用，但对CCL21与GD发生发展的关系知之甚少。本研究旨在检测GD患者血清CCL21水平，探讨骨桥蛋白在调节CCL21生成中的作用。40例初发GD患者，15例甲状腺功能正常的GD患者，12例TRAb阴性的GD患者，25例健康对照。采用酶联免疫吸附试验(EL ISA)检测血浆和培养上清液中CCL21的含量。用抗体包被的磁珠分离外周血单个核细胞中的CD4+T细胞。用定量聚合酶链式反应检测CD4+T细胞CCL21的表达水平。我们首次证实血浆CCL21水平在GD患者中高表达，在TRAb阴性的GD患者中恢复。此外，CCL21水平与TRAb水平和血浆OPN浓度相关。此外，我们还证实了重组OPN以剂量和时间依赖的方式增加CCL21的表达。这些数据表明血浆CCL21水平与GD之间存在临床相关性。CCL21可作为一种新的GD生物标志物，也可作为TRAb阳性GD治疗的潜在靶点。
Graves' disease (GD) is a chronic autoimmune process characterized by the production of auto-antibodies that presumably consequent to the lymphocytic infiltrates in the thyroid. Chemokine (C-C motif) ligand 21 (CCL21) is important for the circulation of CC-chemokine receptor 7 (CCR7)-expressing cells. Meanwhile, osteopontin (OPN) enhances the production of proinflammatory cytokines and chemokines through NF-kappa B and MAPK signaling pathways in GD. Although CCL21 has been reported to play a vital role in several autoimmune diseases, little is known about the relationship between CCL21 and GD development. This study aimed to detect the CCL21 level in GD and to examine the role of OPN in regulating CCL21 production. 40 initial GD patients, 15 euthyroid GD patients, 12 TRAb-negative GD patients, and 25 healthy control donors were recruited. CCL21 levels in plasma and culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). CD4+ T cells were isolated from peripheral blood mononuclear cells using antibody-coated magnetic beads. Quantitative polymerase chain reaction was used to determine CCL21 expression levels in CD4+ T cells. We demonstrated for the first time that plasma CCL21 levels were overexpressed in GD patients and recovered in TRAb-negative GD patients. Moreover, CCL21 levels correlated with TRAb levels and plasma OPN concentrations. Furthermore, we demonstrated that recombinant OPN increased the expression of CCL21 in a dose- and time-dependent manner. These data indicated a clinical correlation between plasma CCL21 levels and GD. CCL21 could serve as a novel biomarker for GD as well as a potential target for TRAb-positive GD treatment.