强直性脊柱炎患者TNF-α与MMP-3的相关性

Correlation between tumor necrosis factor-alpha and matrix metalloproteinase-3 in ankylosing spondylitis patients

  • 摘要: 目的 研究强直性脊柱炎患者中MMP-3与TNF-α之间的作用机制。方法 在体外分别分离出5例AS患者的外周血单个核细胞(PBMC)和6例AS患者的膝关节液中的单个核细胞(SFMC),利用不同浓度人重组MMP-3分别在体外诱导PBMC和SFMC,然后应用ELISA技术检测诱导前后TNF-α浓度变化;同时在分离了7例脊柱关节病(SpA)患者的PBMC后,又进一步分离出它们的贴壁细胞(adherent cells),研究MMP-3是否选择性地作用于单核-巨噬细胞系统还是淋巴细胞系统。结果 不同浓度的MMP-3均能诱导AS患者PBMC释放TNF-α,并且TNF-α的浓度具有剂量依赖性;MMP-3能够明显诱导贴壁细胞分泌TNF-α;MMP-3对SFMC具有一定程度的诱导作用,但同时还观察到与PBMC不同的是,即使没有MMP-3的诱导作用,SFMC自身也能分泌一定程度的TNF-α。结论 AS患者中,MMP-3与TNF-α之间的相互作用可能是参与其发病的重要原因之一,同时MMP-3可能是通过选择性地作用于AS患者的单核-巨噬细胞系统,而非通过淋巴细胞系统来发挥作用。

     

    Abstract: Objective To study the mechanism of action between matrix metalloproteinase-3(MMP-3) and tumor necrosis factor-alpha(TNF-a) in ankylosing spondylitis(AS) patients. Methods After peripheral blood mononuclear cells(PBMC) were isolated from 5 AS patients and synovial fluid mononuclear cells(SFMC) were isolated from 6 AS patients with synovial fluids in their knee joints,the PBMC and SFMC were stimulated in vitro with human recombinant MMP-3 and changes in TNF-α expression were detected by enzyme linked immunosorbent assay(ELISA).(Adherent cells were also isolated from PBMC of 7 patients with spondyloarthropathy(SpA) using(human recombinant MMP-3) stimulated adherent cells in vitro and the concentration of TNF-α was determined by ELISA). Results Different concentrations of human recombinant MMP-3 induced release of TNF-α by stimulating PBMC in vitro in a dose-dependent manner. The SFMC of AS patients could automatically produce TNF-α even though it was not stimulated by human recombinant MMP-3. Conclusion Interaction between MMP-3 and TNF-α may play an important role in the pathogenesis of AS. MMP-3 may also selectively stimulate monocytes or macrophages rather than lymphocytes.

     

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