AP-1 and NF-κB regulation in rheumatoid arthritis and murine collagen-induced arthritis
AP-1 and NF-κB regulation in rheumatoid arthritis and murine collagen-induced arthritis
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DOI：
10.3109/08916939808995367
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发表时间：
1998-01-01
期刊：
影响因子：
3.5
通讯作者：
Firestein, GS
中科院分区：
文献类型：
--
作者：
Han, ZN;Boyle, DL;Firestein, GS
目的探讨核转录因子ap - 1和nf - κ B在小鼠类风湿关节炎和胶原性关节炎中的表达及调控。方法采用电泳迁移位移法（EMSA）和免疫组化检测RA、OA和正常滑膜组织中AP-1、NF-kappa B的表达和功能a。然后在小鼠胶原诱导关节炎（CIA）中检测转录因子表达动力学。免疫后10 ~ 45 d，用CLA小鼠爪核提取物进行emsa测定AP-1和NF-kappa B的结合活性。northern blot检测胶原酶-3 （MMP13）和基质溶解素（MMP3） mRNA的表达。结果免疫组化结果显示，RA和OA滑膜内膜NF-kappa B表达均升高。RA患者的内膜中也存在AP-1成分Jun和Fos， RA患者的nas明显高于OA患者，RA患者的AP-1和nf - κ B的DNA结合活性均明显高于OA患者。在CIA中，AP-1和NF-kappa B的表达在发病前1-2周的第20天升高。结论CIA和RA大鼠AP-1和NF-kappa B的DNA结合活性均显著升高，在CIA中，AP-1和NF-kappa B的激活先于临床关节炎和金属蛋白酶基因的表达。NF-kappa B表达与金属蛋白酶表达的相关性优于AP-1。
Objective To determine the expression and regulation of nuclear transcription factors AP-I and NF-kappa B in rheumatoid arthritis and in collagen-induced arthritis in mice.Methods AP-1 and NF-kappa B expression and function a ere determined in RA, OA and normal: synovial tissue by electrophoretic mobility shift assay (EMSA) and immunohistochemistry. The kinetics of transcription factor expression were then examined in collagen-induced arthritis (CIA) in mice. EMSAs a ere performed with the nuclear extracts obtained from paws of CLA mice from 10 to 45 d after immunization to determine AP-1 and NF-kappa B binding activity. The expression of collagenase-3 (MMP13) and stromelysin (MMP3) mRNA was examined by northern blot analysis.Results Immunohistochemistry showed that NF-kappa B expression was increased in both RA and OA synovial intimal lining. AP-1 components Jun and Fos were also present in the intimal Lining and nas significantly greater in RA than OA, The DNA binding activities of both AP-I and NF-kappa B were significantly higher RA patients compared with OA. In CIA, AP-1 and NF-kappa B expression increased by day 20, which was 1-2 weeks before onset of clinical arthritis. However, collagenase and stromelysin gene expression did not increase until day 35,Conclusion The DNA binding activity of AP-1 and NF-kappa B are markedly increased in both CIA and RA, In CIA, activation of AP-I and NF-kappa B precede both clinical arthritis and metalloproteinase gene expression. NF-kappa B expression correlated better than AP-1 with metalloproteinase expression.