First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China.
Invest Ophthalmol Vis Sci. 2011 Sep 9;52(10):7084-9. doi: 10.1167/iovs.11-7539.
Osteopontin (OPN) is a proinflammatory cytokine involved in chronic inflammatory diseases. This study aimed to analyze the role of OPN in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.
Serum levels of OPN in VKH patients and healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells (PBMCs) or CD4+ T cells were cultured with anti-CD3 and anti-CD28 antibodies in the absence or presence of recombinant OPN for the determination of cell proliferation and cytokines. Cell proliferation was detected using a cell counting kit. Levels of interferon (IFN)-γ and interleukin (IL)-17 were detected by ELISA. Four single nucleotide polymorphisms (SNPs) of OPN and four SNPs of OPN receptors were genotyped in 601 VKH patients and 605 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism assay.
OPN serum levels were significantly higher in patients with active VKH than in patients with inactive VKH and in healthy controls. PBMCs or CD4+ T cells cultured with recombinant OPN induced a marked cell proliferation and profound secretion of IFN-γ and IL-17 from patients with active VKH. A significantly increased frequency of the OPN rs4754 TT genotype (P = 0.004, pc = 0.048) was observed in VKH patients compared with healthy controls. No association could be detected among the four selected SNPs of OPN receptors and VKH.
OPN may be relevant to the pathogenesis of VKH disease. The TT genotype of rs4754 may be a susceptible factor for VKH disease in a Chinese Han population.
骨桥蛋白（OPN）是一种参与慢性炎症性疾病的促炎细胞因子。本研究旨在分析 OPN 在 Vogt-小柳-原田（VKH）病发病机制中的作用。
采用酶联免疫吸附试验（ELISA）检测 VKH 患者和健康对照者血清 OPN 水平。在无或有重组 OPN 的情况下，用抗 CD3 和抗 CD28 抗体培养外周血单个核细胞（PBMC）或 CD4+T 细胞，以测定细胞增殖和细胞因子。用细胞计数试剂盒检测细胞增殖。ELISA 法检测干扰素（IFN）-γ和白细胞介素（IL）-17 水平。采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）法检测 601 例 VKH 患者和 605 例健康对照者 OPN 的 4 个单核苷酸多态性（SNP）和 OPN 受体的 4 个 SNP。
与静止期 VKH 患者和健康对照者相比，活动期 VKH 患者 OPN 血清水平显著升高。用重组 OPN 培养的 PBMC 或 CD4+T 细胞可诱导活动期 VKH 患者明显的细胞增殖和 IFN-γ和 IL-17 的大量分泌。与健康对照者相比，VKH 患者 OPN rs4754 TT 基因型的频率显著升高（P = 0.004，pc = 0.048）。在四个选定的 OPN 受体 SNP 中，未发现与 VKH 之间存在关联。
OPN 可能与 VKH 病的发病机制有关。rs4754 的 TT 基因型可能是汉族人群 VKH 病的易感因素。
