Amelioration of a rat collagen-induced arthritis by treated with AdProTΔNLS

• Main Authors: Shih-Yii Chaung, 莊士億
• Other Authors: C.R. Wang
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/45288505306028851278

碩士 === 國立成功大學 === 生物化學研究所 === 93 === 　　Rheumatoid arthritis is a chronic inflammatory disease characterized with polyarthritis and bone destruction followed with infiltration of monocytes, and T cells into the synovial joints. Inflammatory synovium in the joint lining called pannus invades and destroys local bone structure. Synovial hyperplasia results from a marked increase in macrophages and synoviofibroblasts, locally expressed inflammatory mediators, TNF-�� and IL-1��, and secreted matetalloproteinases, to digest the extracellular matrix in bone. However, those cells also secreted abnormal chemotactic cytokines, RANTES and MIP-1��, are crucial for T cell chemotaxic from the circulation to inflamed tissue and also play an important role in the regulation of transendotherial migration of monocytes. Our laboratory have constructed an adenovirus encoding prothymosin (ProT) deletion mutant lacking the nuclear localization signal (NLS), exhibited a punctured nuclear distribution and reduced cell proliferation. Data of our experiment indicated that MIP-1�� promoter expression was reduced by AdProT�就LS treatment. In this study, we investigated the effect of AdProT�就LS treatment in a rat model of collagen-induced arthritis (CIA). Our resulted showed that the clinical severity of ankle joint arthritis in CIA rats was ameliorated by the AdProTΔNLS treatment in comparison with that of the AdLacZ-injected group. The lower number of the synovial macrophages and a decreased level of macrophage inflammatory protein 1���n(MIP-1���w�z found in the AdProTΔNLS-injected group. Reduced levels of proinflammatory cytokines, TNF-�� and IL-1���nwere observed in the ProTΔNLS gene therapy. The activity of MMP-9 was reduced and the proliferation of lymphocytes was improved by ProTΔNLS gene transfers in CIA animal model. Therefore, these data suggested that suppression of the ProTΔNLS gene therapy in CIA rats may be attributable to the down expression of MIP-1���nin the synovial joints. Thymic peptide, ProTΔNLS, may be used as therapeutic strategy for rheumatoid arthritis pateints.