Human immunodeficiency virus vector-mediated intra-articular expression of angiostatin inhibits progression of collagen-induced arthritis in mice
Human immunodeficiency virus vector-mediated intra-articular expression of angiostatin inhibits progression of collagen-induced arthritis in mice
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DOI：
10.1007/s00296-004-0476-7
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发表时间：
2005-09-01
影响因子：
4
通讯作者：
Shimada, T
中科院分区：
文献类型：
--
作者：
Kato, K;Miyake, K;Shimada, T
我们研究了人类免疫缺陷病毒（HIV）载体介导的血管抑制素局部表达在用牛II型胶原和弗氏完全佐剂免疫产生的小鼠模型中治疗小鼠胶原诱导关节炎的可行性。将含有小鼠血管抑制素表达单元（HIV-angiostatin）的HIV载体注射到关节炎发生后的右膝关节；将含有增强型绿色荧光素蛋白（EGFP）标记基因的HIV载体（HIV-EGFP）注射到左关节内。定量组织学评估显示，该方案确定的右膝关节滑膜细胞增生和滑膜形成明显减少。对同侧爪x线片变化的抑制也被观察到。这些结果表明，HIV载体介导的血管抑制素表达有效抑制胶原诱导关节炎的进展。血管抑制基因治疗可能为有效治疗类风湿性关节炎提供新的途径。
We examined the feasibility of the human immunodeficiency virus (HIV) vector-mediated local expression of angiostatin in the treatment of murine collagen-induced arthritis in a mouse model generated by immunization with bovine type II collagen and Freund's complete adjuvant. The HIV vector containing the murine angiostatin expression unit (HIV-angiostatin) was injected into right knee joints after arthritis development; the HIV vector containing the enhanced green fluorescein protein (EGFP) marker gene (HIV-EGFP) was injected into the left joints. Quantitative histological evaluation demonstrated that synovial cell hyperplasia and pannus formation were significantly reduced in the right knee joints as determined by this protocol. Suppression of radiographical changes in the ipsilateral paws was also observed. These results indicate that the HIV vector-mediated expression of angiostatin efficiently inhibits the progression of collagen-induced arthritis. Angiostatic gene therapy may provide a new approach to the effective treatment of rheumatoid arthritis.