| 摘要 |
<p>The onset ratios and pathological conditions of collagen-induced arthritis (CIA) and adjuvant arthritis (AA) in model mice and rats, respectively, are successfully ameliorated by topically expressing the cyclin-dependent kinase inhibitors (CDKI), p16<1NK4a> and p21<Cip1> proteins in articular tissues using adenoviral vectors. In the synovial cells of the CDKI transduced mice, the expression of inflammatory cytokines (IL-1 beta , IL-6, TNF- alpha , etc.) was inhibited. The present invention provides the use of the p21<Cip1> protein for inhibiting the abnormal proliferation of synovial tissues, inflammation in synovial tissues and/or the expression of inflammatory cytokines in synovial-tissues; the p21<Cip1> gene; compounds promoting the activity or expression of the p21<Cip1> protein; and pharmaceutical compositions containing these molecules. Furthermore, the present invention provides method of screening for compounds participating in the abnormal proliferation of synovial tissues, inflammation in synovial tissues and/or the expression of inflammatory cytokines in synovial tissues targeting the p21<Clip1> protein. Rheumatoid arthritis and the like can be prevented or treated by, for example, gene therapy using p21<Clip1>.</p> |
