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目的观察细胞外基质金属蛋白酶诱导剂(EMMPRIN/CD147)对类风湿关节炎(RA)患者滑膜成纤维细胞(FLS)合成基质金属蛋白酶(MMPs)的作用。方法手术切除的RA患者的滑膜组织,分离成FLS,传代培养。明胶酶谱法测FLS的MMPs含量。将FLS与高表达EMMPRIN/CD147的单核细胞株(THP)-1共培养,观察THP-1细胞对FLS MMPs表达量的影响,同时观察EMMPRIN/CD147拮抗肽激活蛋白(AP)-9对FLS MMPs表达的影响。结果THP-1细胞表达高水平的CD147,而MMP-2、MMP-9的表达水平很低;分离的FLS表达低水平的CD147和一定水平的MMP-2、MMP-9。二者混合培养后,FLS表达MMP-2、MMP-9水平显著升高,随着THP-1细胞数的增加,MMP-2、MMP-9的合成量也增加。THP-1对FLS合成MMP-2、MMP-9的刺激作用可被CD147拮抗肽AP-9所抑制。结论CD147对RA患者FLS合成MMP-2、MMP-9有刺激作用,而这种刺激作用可被CD147拮抗肽AP-9所抑制。
Objective To investigate the effect of extracellular matrix metalloproteinase inducer (EMMPRIN / CD147) on the synthesis of matrix metalloproteinases (MMPs) in synovial fibroblasts (FLS) of patients with rheumatoid arthritis (RA). Methods The synovial tissue of RA patients who underwent surgical resection was separated into FLS and subcultured. Gelatin zymography assay of FLS MMPs content. FLS was co-cultured with monocyte strain (THP) -1 with high expression of EMMPRIN / CD147 to observe the effect of THP-1 cells on the expression of FLS MMPs, and to observe the effect of EMMPRIN / CD147 antagonist activating protein (AP) MMPs expression. Results THP-1 cells expressed high level of CD147, while the expression of MMP-2 and MMP-9 was low. Isolated FLS expressed low level of CD147 and certain levels of MMP-2 and MMP-9. After mixed culture, the levels of MMP-2 and MMP-9 in FLS were significantly increased. With the increase of THP-1 cell number, the synthesis of MMP-2 and MMP-9 also increased. THP-1 on FLS synthesis of MMP-2, MMP-9 stimulation can be CD147 antagonist AP-9 inhibition. Conclusion CD147 may stimulate the synthesis of MMP-2 and MMP-9 by FLS in patients with RA, and this stimulation may be inhibited by CD147 antagonist AP-9.