Liu Yun-Xia, Wang Hong, Peng Xiao-Yan, Zhou Zeng-Chao
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing 100730, China.
Zhonghua Yan Ke Za Zhi. 2009 Nov;45(11):1015-9.
To investigate suppressor of cytokine signaling (SOCS) mRNA and protein expression in peripheral blood mononuclear cells (PBMC) of patients with Vogt-Koyanagi-Harada (VKH) disease.
Blood samples were taken from 15 VKH patients with active uveitis, 17 quiescent patients and 16 healthy individuals. IFN-gamma, IL-12 and IL-4 in the serum were measured by ELISA. PBMC were subjected to analysis of SOCS mRNA and protein expression using quantitative RT-PCR and western blot, respectively.
The level of IL-4 in the serum of VKH patients and in controls were (28.40 +/- 5.93) ng/L, (34.5 +/- 9.47) ng/L and (11.25 +/- 4.43) ng/L, IL-12 were (24.33 +/- 8.55) ng/L, (11.53 +/- 6.11) ng/L and (5.19 +/- 2.43) ng/L, IFN-gamma were (18.05 +/- 2.23) ng/L, (15.53 +/- 2.63) ng/L and (1.61 +/- 3.47) ng/L, respectively. The level of IFN-gamma, IL-12 and IL-4 were all significantly higher in the serum of VKH patients than in controls(P < 0.01). IL-4 in quiescent patients was higher than in active patients (P < 0.01), IL-12 and IFN-gamma were lower in quiescent patients was higher than in active patients (P < 0.01, P < 0.05). Cytokine inducible SH2 containing protein (CIS) mRNA, SOCS1 mRNA, SOCS2 mRNA, SOCS3 mRNA and SOCS5 mRNA levels in PBMC of VKH patients with active uveitis are 0.72, 4.92, 1.09, 0.75 and 1.15 folds than that in healthy volunteers, respectively. They are 1.15, 2.25, 1.40, 0.69 and 1.16 folds in static patients, respectively. Marked decreased expression of CIS protein is detected in both active and quiescent patients with no significant difference between two groups (both P < 0.01). SOCS1 protein is up-regulated significantly in active patients compares to in quiescent patients nor in healthy volunteers (P < 0.01, P < 0.05). SOCS3 protein is significantly decreased in patients than in controls (both P < 0.05). SOCS5 protein is much higher in patients than in controls (both P < 0.01), and even higher in quiescent patients than in active episode (P < 0.05).
Up regulation of SOCS1 and SOCS5 expression and down-regulation of SOCS3 and CIS may correlate with the development of a Th1 mediated immune response in VKH disease. There is insidious inflammation in VKH patients with clinically quiescent uveitis, and this may be one of the causes of persistence and recurrences of uveitis.
研究葡萄膜大脑炎(VKH)患者外周血单个核细胞(PBMC)中细胞因子信号转导抑制因子(SOCS)mRNA和蛋白的表达。
采集15例活动期葡萄膜炎VKH患者、17例静止期患者及16例健康个体的血样。采用酶联免疫吸附测定法(ELISA)检测血清中γ干扰素(IFN-γ)、白细胞介素-12(IL-12)和白细胞介素-4(IL-4)的水平。分别采用定量逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法检测PBMC中SOCS mRNA和蛋白的表达。
VKH患者血清中IL-4水平分别为(28.40±5.93)ng/L、静止期患者为(34.5±9.47)ng/L、健康个体为(11.25±4.43)ng/L;IL-12水平分别为(24.33±8.55)ng/L、(11.53±6.11)ng/L和(5.19±2.43)ng/L;IFN-γ水平分别为(18.05±2.23)ng/L、(15.53±2.63)ng/L和(1.61±3.47)ng/L。VKH患者血清中IFN-γ、IL-12和IL-4水平均显著高于健康对照(P<0.01)。静止期患者IL-4水平高于活动期患者(P<0.01),静止期患者IL-12和IFN-γ水平低于活动期患者(P<0.01,P<0.05)。活动期葡萄膜炎VKH患者PBMC中细胞因子诱导含SH2蛋白(CIS)mRNA、SOCS1 mRNA、SOCS2 mRNA、SOCS3 mRNA和SOCS5 mRNA水平分别是健康志愿者的0.72、4.92、1.09、0.75和1.15倍。静止期患者分别为1.15、2.25、1.40、0.69和1.16倍。活动期和静止期患者均检测到CIS蛋白表达明显降低,两组间无显著差异(均P<0.01)。与静止期患者及健康志愿者相比,活动期患者SOCS1蛋白显著上调(P<0.01,P<0.05)。患者SOCS3蛋白水平显著低于对照(均P<0.05)。患者SOCS5蛋白水平显著高于对照(均P<0.01),且静止期患者高于活动期(P<0.05)。
SOCS1和SOCS5表达上调以及SOCS3和CIS表达下调可能与VKH病中Th1介导的免疫反应的发生有关。临床静止期葡萄膜炎的VKH患者存在隐匿性炎症,这可能是葡萄膜炎持续存在和复发的原因之一。