钙黏素11在类风湿性关节炎滑膜组织中的表达及其与炎症的关系  

Expression of cadherin-11 in rheumatoid arthritis synovium and its correlation with inflammation

作　　者：丁孝权[1] 黄越龙[1] 刘松洋[1] 吕厚山[1] 林剑浩[1] 孙铁铮[1] 

机构地区：[1]北京大学人民医院关节病诊疗研究中心,北京100044

出　　处：《细胞与分子免疫学杂志》2014年第12期1295-1299,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(30801160)

摘　　要：目的探讨类风湿性关节炎(RA)滑膜钙黏素11(cadherin-11)的表达与滑膜炎症的相关性及炎性因子对RA滑膜成纤维样细胞(RAFLS)钙黏素11表达的调节效应。方法收集28例行全膝关节置换术的RA患者的滑膜,HE染色后对滑膜炎症进行Rooney评分,免疫组织化学染色检测滑膜钙黏素11的表达,分析钙黏素11表达与滑膜炎性评分及系统性炎症指标的相关性。实时定量PCR和Western blot法检测不同浓度转化生长因子β(TGF-β)或白细胞介素17(IL-17)刺激后RAFLS钙黏素11表达的变化。结果不同C-反应蛋白分层的RA患者滑膜炎性评分无统计学差异。RA滑膜衬里层及衬里下层钙黏素11的表达均与D-二聚体、衬里层厚度、新生血管增多、血管周围淋巴细胞浸润、淋巴细胞滤泡样浸润、淋巴细胞弥散浸润呈正相关,衬里层钙黏素11的表达与间质纤维化呈负相关。经TGF-β或IL-17刺激后RAFLS钙黏素11的mRNA及蛋白表达均上调。结论 RA滑膜钙黏素11的表达明显增加,与滑膜衬里层厚度、新生血管增多及淋巴细胞浸润等密切相关。TGF-β和IL-17可以诱导RAFLS钙黏素11的表达增加。Objective To explore the pattern of cadherin-11 expression and its relationship with synovial inflammation in rheumatoid arthritis（ RA）,and study the regulatory effects of cytokines on cadherin-11 expression on RA fibroblast-like synoviocytes（RAFLS）. Methods Synovium samples were obtained from 28 RA patients who were undergoing total knee replacement. After HE staining,synovitis score was determined according to Rooney＇s inflammation score system. The expression of cadherin-11 in RA synovium was semi-quantified by immunohistochemical staining,and its correlations with Rooney＇s inflammation score and systematic inflammatory markers were analyzed statistically. After induction with transforming growth factor β（ TGF-β） or interleukin 17（ IL-17） at a series of concentrations,the expression of cadherin-11 on RAFLS was assessed by real time guantitative-PCR and Western blotting. Results There was no significant difference in cadherin-11 expression in RA synovium among different levels of C-reactive protein. Cadherin-11 in the lining and sublining layers were positively correlated with D-dimer,synovial lining layer hyperplasia,proliferating blood vessels,perivascular infiltration of lymphocytes,focal aggregation of lymphocytes and diffuse infiltration of lymphocytes; cadherin-11 in the lining layer was negatively correlated with interstitial fibrosis. TGF-β or IL-17 stimulation could up-regulate cadherin-11 expression on RAFLS at mRNA and protein levels. Conclusion The over-expression of cadherin-11 in RA was correlated with synovial lining layer hyperplasia,proliferating blood vessels and infiltration of lymphocytes. Cadherin-11 expression on RAFLS could be induced by TGF-β and IL-17 induction.

关 键 词：钙黏素11 类风湿性关节炎 滑膜炎 转化生长因子Β 白细胞介素-17 

分 类 号：R593.22[医药卫生—内科学] R392.12[医药卫生—临床医学]