骨桥蛋白拮抗干扰素-γ诱导的甲状腺细胞趋化因子分泌

Osteopontin inhibits interferon-γ-induced expression of chemokine in thycocytes

目的 探讨骨桥蛋白（OPN）对干扰素-γ（IFN-γ）诱导甲状腺细胞分泌趋化因子（C-X-C结构域）配体9（CXCL9）的影响及其在Graves病发生发展中的意义。方法 取10例Graves病患者及9名正常对照者手术切除甲状腺组织标本，分离培养Graves病患者及正常对照者的甲状腺原代细胞，通过实时荧光定量PCR技术，比较两者CXCL9及OPN的表达情况。体外培养人正常甲状腺细胞系Nthy-ori3-1和正常人甲状腺原代细胞，分别用不同浓度的OPN及IFN-γ进行刺激实验，利用实时荧光定量PCR技术，检测甲状腺细胞趋化因子CXCL9的mRNA表达情况。结果 Graves病患者与正常对照者甲状腺组织中均存在OPN及CXCL9的表达，与正常对照者比较，Graves病患者甲状腺组织高表达CXCL9及OPN（P〈0.05）。IFN-γ可诱导正常甲状腺细胞系Nthy-ori3-1和人甲状腺原代细胞表达CXCL9（P〈0.01），单独的OPN刺激对CXCL9的表达无明显影响。OPN呈浓度依赖性抑制IFN-γ诱导人正常甲状腺细胞系Nthy-ori3-1分泌趋化因子CXCL9（P〈0.01），并在一定程度上抑制IFN-γ诱导人甲状腺原代细胞分泌趋化因子CXCL9，但差异无统计学意义（P〉0.05）。结论 Graves病中，甲状腺局部OPN表达升高，可能通过与其他促炎因子相拮抗而起到保护作用，这可能是机体的一种代偿反应。

Objective To investigate the effect of osteopontin （ OPN ） on interferon-γ （IFN-γ） -induced expression of chemokine （ C-X-C motif） ligand 9 （CXCL9） in thyrocytes and its significance in the development of Graves＇ disease. Methods Surgical tissues were obtained from ten patients with Graves＇ disease and nine normal controls, and the tissues were prepared for thyroid follicular ceils. The expression of OPN and CXCL9 genes were detected by realtime quantitative PCR. The expression of CXCL9 genes in cultured Nthy-ori3-1 cell line and human thyrocytes stimulated by IFN-γ and OPN were also determined by realtime quantitative PCR. Results Compared to normal controls, CXCL9 and OPN gene levels were significantly higher in Graves＇ disease thyroid tissues （P〈0.05）. OPN inhibited IFN-γ-induced CXCL9 expression in Nthy-ori3-1 cell line in a concentration dependent manner （ P〈0. 01 ）, while inhibited the expression in human thyrocytes to a certain extent but showed no difference （P 〉 0.05 ）. Conclusion The higher expression of OPN in thyroid tissue of Graves＇ disease may antagonize other proinflammtory eytokines, indicating that it may play a protective role and be a compensatory reaction to autoimmune response.