HMGB1在类风湿性关节炎发病中的作用及其机制  

Role and mechanisms of HMGB1 in the pathogenesis of rheumatoid arthritis

作　　者：李康[1] 熊思东[1] 

机构地区：[1]复旦大学免疫生物学研究所,免疫学系,上海硕士研究生200032

出　　处：《国际免疫学杂志》2007年第6期401-404,共4页International Journal of Immunology

基　　金：上海市优秀学科带头人计划(04XD14003)

摘　　要：高迁移率族蛋白1(HMGB1)是一种普遍存在于真核细胞中的染色体蛋白。早期研究证实,HMGB1可作为 DNA 结合蛋白参与维持 DNA 构象和核小体结构的稳定,也可作为一种非特异性的转录因子参与基因表达的调控。近期研究发现,HMGB1可于细胞外分泌释放,参与细胞的分化、迁移和再生,并可介导多种炎性和自身免疫性疾病的发病。特别在类风湿性关节炎(RA)患者及实验性关节炎动物关节局部 HMGB1的表达明显上调,深入研究揭示这些异常表达的 HMGB1可通过多种分子机制在关节炎发病的多个环节中发挥作用,以介导慢性炎症的持续和局部组织的侵蚀破坏,通过阻断和抑制 HMGB1的作用可明显减轻和改善关节炎的症状。这为阐明 RA 的发病机制提供了新的思路,并为 RA 的治疗提供了新的靶点。High mobility group box chromosomal protein 1 （HMGB1）, a highly conserved and ubiquitous nuclear protein in nearly all eukaryotic cells, was originally identified as a nuclear DNA-binding protein that served as a structural cofactor critical for proper transcriptional regulation and gene expression. Recent stud- ies indicated that immune cells could liberate HMGB1 into the extracellular milieu where it functioned as a proinflammatory cytokine. The role for HMGB1 protein in arthritis was established by the observations of up- regulated expression of HMGB1 in synovial tissue of patients with rheumatoid arthritis as well as in the joints of animals used to model arthritis. A growing body of evidence has demonstrated that the aberrant HMGB1 expression played an important role in both inflammatory and destructive processes in the pathophysiology of arthritis. Furthermore, in the mouse model of rheumatoid arthritis, HMGB1 blockade and inhibition could attenuate joint inflammation and damage. These studies identify a novel pathway in the pathogenesis of inflammatory arthritis, as well as a new target for biologic therapy.

关 键 词：高迁移率族蛋白1 关节炎 类风湿 发病机制 

分 类 号：R593.22[医药卫生—内科学]