摘要
目的:探讨高迁移率族蛋白(HMGB)1在类风湿关节炎(RA)病情活动中的作用机制。方法:选取RA患者74例(活动期38例、非活动期36例)及健康对照者26例。采用RT-PCR方法检测外周血单个核细胞(PBMC)中HMGB1 mRNA的表达,酶联免疫吸附(ELISA)方法检测血清中HMGB1蛋白的表达。采用流式细胞术分析CD14+单核细胞表面Toll样受体(TLR)4和EMMPRIN/CD147的表达。结果:活动期RA组HMGB1 mRNA相对表达量和蛋白水平均高于健康对照者和非活动期RA患者[分别为2.63 vs 0.71,0.93和(10.20±1.24 vs 7.48±1.75,8.31±1.85)ng/ml)](P<0.01)。活动期RA患者CD14+单核细胞上TLR4和CD147的表达量均显著高于非活动期和健康对照组(P<0.01),非活动期患者显著高于健康对照组(P<0.01)。TLR4和CD147双阳性细胞数量和蛋白的相对表达量在活动期RA患者中均最高。血清中HMGB1蛋白水平与ESR、CRP、RF、及关节X线分期均呈正相关,亦与TLR4和CD147的表达呈正相关(P<0.05或P<0.01)。结论:RA患者PBMC具有合成和分泌HMGB1蛋白的功能。HMGB1可能通过与TLR4结合激活CD14+单核细胞并表达CD147,促进其向滑膜组织迁移而加速骨质破坏。
Objective： To investigate the role and possible mechanism of high mobility group box （HMGB） 1 in the development and progress of rheumatoid arthritis（RA）.Methods：PBMC and serum samples were obtained from 74 RA patients （38 in active stage and 36 in sta- ble stage） and 26 health controls. The expression of HMGB1 mRNA and protein was detected by RT-PCR and ELISA. Flow cytometric analysis （FCM） was used to detect the expression of Toll-like receptor 4 and CD147 on CD14^＋ monocytes. Results： The expression of HMGB1 mRNA and protein in active RA was significantly higher than those in health controls and inactive RA [ 2.63 vs 0. 71,0.93 and （ 10.20 ± 1.24 vs 7.48 ± 1.75,8.31 ± 1.85） ng/ml, respectively] （P 〈 0.01）. The expression of TLR4 and CD147 on CD14 ^＋ monocytes in active RA patients was significantly increased than those in inactive RA and healthy controls（ P 〈 0.01）.They were also higher in inactive RA than in healthy controls（ P 〈 0.01 ）. The expression TLR4^＋ CD147^＋ monocytes was highest in active patients（ P 〈 0.05 or P 〈 0.01 ）. Level of HMGB1 protein in sermn of RA patients was positively correlated with ESR, CRP, RF, radiographic phase, so did it with TLR4 and CD147. Conclusion： HMGB1 could be synthesized and released from PBMC of active RA patients. HMGB1 maybe binds to TLR4 of CD14^＋ monocytes to promote CD147 expression, and induced activity of disease, even bone erosion.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2009年第7期662-665,共4页
Chinese Journal of Immunology
基金
河北省科技厅科技攻关基金(No.08206122D)资助项目
关键词
关节炎
类风湿
高迁移率族蛋白
TOLL样受体
胞外基质金属蛋白酶诱导因子
Arthritis
Rheumatoid
High mobihty group box chromosomal protein
Toll-like receptor
Extracellular matrix metalloproteinase inducer
