Graves病患者血清TLR4、NF-κB 和Treg/Th17相关细胞因子表达变化及意义

Involvement of circulating TLR4, NF-kB and Treg/Th17 related cytokines in Graves' disease

摘要:

目的探讨Graves 病患者血清Toll 样受体4（TLR4）、核因子-κB（NF-κB）和调节性T细胞/ 辅助性T细胞17（Treg/Th17）相关细胞因子表达变化及意义。方法选取62 例初步确诊为Graves 病的患者和45 例健康者（对照组），采用电化学发光法检测血清中促甲状腺素（TSH）、游离三碘甲状腺原氨酸（FT3）、游离四碘甲状腺原氨酸（FT4）和促甲状腺素受体抗体（TRAb）水平，利用双抗体酶联免疫吸附试验（ELISA 法）对血清中TLR4、NF-κB、TGF-β1、IL-10、IL-6 和IL-17 水平进行检测。结果Graves病患者血清TSH水平低于对照组，而血清FT3、FT4 和TRAb 水平则高于对照组，差异有统计学意义（P <0.05）；Graves 病患者血清TLR4、NF-κB、IL-10、IL-6 和IL-17 水平均高于对照组，而TGF-β1水平则低于对照组，差异有统计学意义（P <0.05）；Pearson 相关分析显示，Graves 病患者血清TSH 与TLR4、NF-κB、IL-10、IL-6 和IL-17 均呈负相关（P<0.05） ，而与TGF-β1 呈正相关（P <0.05），血清FT3 和FT4 均与TLR4、NF-κB、IL-10、IL-6 和IL-17呈正相关（P <0.05），而与TGF-β1呈负相关（P <0.05）；Graves病患者血清TLR4与NF-κB呈正相关（P <0.05），且与IL-10、IL-6 和IL-17 呈正相关（P <0.05），而与TGF-β1呈负相关（P <0.05）。结论Graves 病患者血清TLR4、NF-κB、IL-10、IL-6和IL-17水平升高，而TGF-β1水平降低，NF-κB信号通路激活和Treg/Th17平衡失调可能共同参与Graves 病发病过程。

Abstract:

Objective To investigate the concentration of Toll-like receptor 4 (TLR4), nuclear factor kB(NF-kB) and regulatory T cells (Treg) / T helper cell 17 (Th17) related cytokines in patients with Graves' disease and their potential correlations. Methods A total of 62 patients initially diagnosed with Graves'disease and 45 healthy volunteers were involved in this study. The serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4) and thyrotropin receptor antibody (TRAb) were measured by Electrochemiluminescence. The serum levels of TLR4, NF-kB, transforming growth factor β(TGF-β), interleukin 10 (IL-10), interleukin 6 (IL-6) and interleukin 17 (IL-17) were measured by enzymelinked immunosorbent assay (ELISA). Results The serum levels of TSH in patients were increased while FT3,FT4 and TRAb were decreased significantly when compared with those in volunteers (p < 0.05). Blood concentration of TLR4, NF-kB, IL-10, IL-6 and IL-17 in patients was upregulated while concentration of TGF-β1 was downregulated in comparison with the healthy control group (p < 0.05). Pearson correlation analysis showed that TSH was negatively correlated with TLR4, NF-kB, IL-10, IL-6 and IL-17 (p < 0.05),but positively correlated with TGF-β1 (p < 0.05). FT3 and FT4 were positively correlated with TLR4, NF-kB,IL-10, IL-6 and IL-17, but negatively correlated with TGF-β1 (p < 0.05). TLR4 was positively correlated with NF-kB, IL-10, IL-6 and IL-17 (p < 0.05), but negatively correlated with TGF-β1 (p < 0.05). Conclusions The serum levels of TLR4, NF-kB, IL-10, IL-6 and IL-17 in patients with Graves' disease are increased while level of TGF-β1 is decreased. Activation of NF-kB signaling pathway and Treg/Th17 imbalance might be involved in the pathogenesis of Graves' disease.