原发性胆汁性肝硬化患者树突状细胞中细胞因子及其信号转导抑制分子变化的意义

Expression of cytokines and suppressor of cytokine signaling in peripheral blood mononuclear cells derived dendritic cells from primary biliary cirrhosis patients

目的观察细胞因子信号转导抑制分子（SOCS）在原发性胆汁性肝硬化（PBC）患者树突状细胞（DC）及其表型和分泌细胞因子的变化，以研究SOCS在PBC发病机制中的作用。方法对10例PBC患者和8名健康人，用流式细胞术（FCM）分析其DC表型CD83、CD86和人类白细胞抗原DR（HLA—DR），用酶联免疫吸附测定法（ELISA）检测DC培养上清液中细胞因子白细胞介素一10（IL一10）、IL—12和干扰素-y（IFN-y）含量，用免疫印迹法（WB）测定DC中SOCSl和SOCS3水平；并评价分析这些指标在2组中的变化特征。结果PBC患者外周血中DC细胞表型CD83、CD86和HLA—DR的表达率分别为（79．4±4．8）％、（86．5±6．3）％和（90．0±3．5）％，均高于健康对照组的表达率[（68．3±4．1）％、（74．24-6．3）％和（83．6±7．6）％，t值分别为5．340、4．120和2．514，P均〈0．05]；DC分泌的IL．12和IFN-y含量分别为（53．54-11．1）、（32．04-9．0）ng／L，与健康对照组的细胞因子含量[（32．1±10．7）、（15．4±8．1）ng／L]相比，IL-12和IFN-1均显著升高（t值分别为4．123和3．818，P均〈0．01）；IL一10含量为（7．0±4．6）ng／L，与健康对照组[（5．8±4．2）ng／L]相比，差异无统计学意义（t=0．563，P〉0．05）；WB检测PBC组DC中SOCSl和SOCS3的表达比健康对照组明显降低。结论PBC患者体内DC更倾向于成熟状态，其抗原递呈能力明显增强，SOCS的低表达可能与免疫平衡紊乱和免疫耐受破坏有关。r手华检验医学杂志，2012，35：216-220）

Objective To study the role of suppressor of cytokine signaling （SOCS）in the pathogenesis of primary biliary cirrhosis（ PBC ） , the levels of SOCS protein and the changes of function of dendritic cell（DC） were respectively observed from PBC patients. Methods The study population consisted of 10 patients of PBC and 8 healthy controls. Phenotypic analysis of cultured peripheral blood mononuclear cells （PBMC）-derived DC was performed by flow cytometry （FCM）, such as CD83, CD86 and human leukocyte antigen DR（HLA-DR）. The levels of iuterleukin-10 （IL-10） , interferon-~ （ IFN-7 ） and IL-12 in culture supernatant of DC were measured by enzyme linked immunosorbent assay （ ELISA ） . The protein levels of SOCS1 and SOCS3 were detected by Western blot （ WB ） . The features of changes in these parameters were analyzed between the two groups. Results The expression of CD83, CD86 and HLA-DR in PBC patients were （79.4 ±4. 8 ） % , （ 86. 5 ± 6. 3 ） % and （ 90. 0 ± 3.5 ） % , which were significantly higher than those in healthy control group[ （68.3 _＋4. 1）%, （74. 2 ±6. 3）% and （83.6 ＋7.6）% ], respectively （t =5. 340,4. 120,2. 514,P 〈0. 05）. The levels of IL-12 and IFN-y/ in PBC patients were （53.5 ±11.1 ）and （32. 0 ＋9. 0） ng/L, which were significantly higher than those in healthy control group[ （32. 1 ± 10. 7） and （15.4 ±8.1 ） ng/L; t = 4. 123,3. 818 ,P 〈 0.011. There were not any significant difference of IL-10 level between PBC patients [ （ 7.0 ± 4. 6 ） ng/L ] and the healthy controls [ （ 5.8 ± 4. 2 ） ng/L ;t -- 0. 563, P 〉 0. 05 ]. The proteins levels of SOCS1 and SOCS3 in PBMC-derived DC from PBC group were decreased significantly than those in healthy control group. Conclusions The results suggest that the PBMC-derived DC in PBC patients has greater ability of potent maturation and antigen presentation function. The decreased expression of SOCS levels may be associated with the excessive immunological reaction and the breakdown of self-tolerance. （Chin J Lab Med, 2012,35：216-220）