阿巴西普通过抑制成纤维样滑膜细胞的迁移来缓解类风湿关节炎的发展，其作用机制与 MAPK 通路有关。
Abatacept alleviates rheumatoid arthritis development by inhibiting migration of fibroblast-like synoviocytes via MAPK pathway.
机构信息
Department of Rheumatology, Yantaishan Hospital, Yantai, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):3105-3111. doi: 10.26355/eurrev_201904_17594.
OBJECTIVE
To investigate whether Abatacept could regulate the occurrence and progression of rheumatoid arthritis (RA) by mediating cell migration of fibroblast-like synoviocytes (FLS) via mitogen-activated protein kinase (MAPK) pathway.
PATIENTS AND METHODS
Levels of MMP1, MMP3 and MMP13 in RA-FLS treated with Abatacept or MAPK pathway inhibitor were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The regulatory effect of Abatacept on MAPK pathway was detected by Western blot. Transwell assay was performed to access the role of Abatacept in regulating cell migration of RA-FLS.
RESULTS
Abatacept treatment remarkably downregulated levels of MMP1, MMP3 and MMP13 in FLS, which were confirmed by qRT-PCR and ELISA. Migratory ability of FLS was inhibited by Abatacept treatment. Western blot results suggested that Abatacept treatment downregulated MAPK pathway-related genes in FLS. The effects of Abatacept on MMPs expressions and cell migration were partially reversed by SB203580 treatment, the MAPK pathway inhibitor.
CONCLUSIONS
Abatacept inhibits FLS migration and MMPs expressions via inhibiting MAPK pathway, thereby inhibiting RA development.
目的
通过研究 Abatacept 是否可以通过丝裂原活化蛋白激酶（MAPK）通路调节成纤维样滑膜细胞（FLS）的细胞迁移来调节类风湿关节炎（RA）的发生和进展。
方法
采用定量实时聚合酶链反应（qRT-PCR）和酶联免疫吸附试验（ELISA）检测 Abatacept 或 MAPK 通路抑制剂处理的 RA-FLS 中 MMP1、MMP3 和 MMP13 的水平。采用 Western blot 检测 Abatacept 对 MAPK 通路的调节作用。通过 Transwell 实验评估 Abatacept 对 RA-FLS 细胞迁移的调节作用。
结果
Abatacept 处理可显著下调 FLS 中 MMP1、MMP3 和 MMP13 的水平，qRT-PCR 和 ELISA 结果均证实了这一点。Abatacept 处理可抑制 FLS 的迁移能力。Western blot 结果表明，Abatacept 处理可下调 FLS 中 MAPK 通路相关基因的表达。MAPK 通路抑制剂 SB203580 部分逆转了 Abatacept 对 MMPs 表达和细胞迁移的影响。
结论
Abatacept 通过抑制 MAPK 通路抑制 FLS 的迁移和 MMPs 的表达，从而抑制 RA 的发展。
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