CD147与类风湿关节炎成纤维样滑膜细胞MMPs合成的关系

目的观察类风湿性关节炎(rheumatoid arthritis, RA)患者成纤维样滑膜细胞(fibroblast-like synoviocytes, FLS)与高表达CD147的单核细胞株(THP-1)共培养后,基质金属蛋白酶(matrix metalloproteinases,MMPs)合成的变化.方法从手术切除的RA患者滑膜组织中,分离FLS,经流式细胞术测定CD14,CD68及免疫组化测定波形纤维蛋白(vimentin)证实后,传代培养.将FLS与高表达 CD147的THP-1共培养,观察THP-1细胞对FLS MMPs合成的影响.用明胶酶谱法测FLS MMP-2,MMP-9含量.同时观察CD147拮抗肽(AP9)对MMPs表达的影响.结果高表达CD147,低表达MMP-2、 MMP-9的THP-1细胞与CD147表达水平低的RA FLS混合培养后,FLS合成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.结论高表达CD147的THP-1细胞对共培养的RA FLS合成MMP-2、MMP-9有刺激作用,这种刺激作用可被CD147拮抗肽AP-9所抑制,提示THP-1表面的CD147对FLS合成MMPs有促进作用.

Enhanced production of MMP-2, MMP-9 by fibroblast cells from rheumatoid arthritis patients when co-cultured with monocytes of high CD147 expression

Objective To study the stimulating effects of CD147 on the production of MMPs by fibroblast cells isolated from rheumatoid arthritis patients.Methods Fibroblast cells were isolated from synovial tissues excised from rheumatoid arthritis patients during synovectomy,and confirmed by detection of CD147,CD68 with flow cytometry(FCM) and vimentin protein by immunostaining(SP).The fibroblast-like synoviocytes(FLS) were co-cultured with THP-1 cells(a cell line of monocytes) with high levels of CD147.The production of MMP-2,MMP-9 by synovial fibroblasts was evaluated by Gelatin zymography and RT-PCR.The expression of CD147 on THP-1 cells and synovial fibroblasts was detected by FCM.Antagonist peptide to CD147 AP-9 was used to study the effects on MMPs production.Results The isolated synovial fibroblasts characterized by negative expression of CD14,CD 68 and positive expression of vimentin protein,expressed low levels of CD147 and high levels of MMP-2 and MMP-9,while THP-1 cells expressed much higher levels of CD147 and lower levels of MMP-2,MMP-9.When the synovial fibroblasts were co-cultured with THP-1,the production of MMP-2,MMP-9 by FLS was enhanced,but when co-cultured with the antagonist peptide(AP-9) of CD147,it was suppressed.Conclusion The ability of MMP-2,MMP-9 production by synovial fibroblasts was enhanced when co-cultured with THP-1 of high levels of CD147,and the enhancement can be suppressed by the antagonist peptide(AP-9) of CD147.