The Role of Raf Kinase Inhibitor Protein in Rheumatoid Fibroblast-like Synoviocytes Invasiveness and Cytokine and Matrix Metalloproteinase Expression

被引：27

作者：

Ahn, Joong Kyong ^{[2
]}

Hwang, Ji-Won ^{[1
]}

Bae, Eun-Kyung ^{[3
]}

Lee, Jaejoon ^{[1
]}

Jeon, Chan Hong ^{[4
]}

Koh, Eun-Mi ^{[1
]}

Cha, Hoon-Suk ^{[1
]}

机构：

[1] Sungkyunkwan Univ, Dept Med, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea

[2] Sungkyunkwan Univ, Dept Internal Med, Kangbuk Samsung Hosp, Sch Med, Seoul 135710, South Korea

[3] Sungkyunkwan Univ, Ctr Mol Med, Samsung Biomed Res Inst, Sch Med, Seoul 135710, South Korea

[4] Soonchunhyang Univ, Coll Med, Dept Internal Med, Seoul, South Korea

来源：

INFLAMMATION | 2012年 / 35卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

raf kinase inhibitor protein; rheumatoid arthritis; fibroblast-like synoviocytes; matrix metalloproteinase; cytokines; PROSTATE-CANCER; SYNOVIAL FIBROBLASTS; JOINT DESTRUCTION; ARTHRITIS; CELLS; SUPPRESSION; METASTASIS; RKIP; SYSTEM;

D O I：

10.1007/s10753-011-9336-2

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Fibroblast-like synoviocytes (FLS) play an important role in the pathogenesis of rheumatoid arthritis. Raf kinase inhibitor protein (RKIP) negatively regulates the Raf/MEK/ERK and NF-kappa B pathway. The role of RKIP in rheumatoid FLS is unknown. The purpose of the present study was to investigate the function of RKIP in rheumatoid FLS. Rheumatoid FLS were transfected with either RKIP-expressing plasmids or RKIP small interfering RNA (siRNA). RKIP protein was detected in rheumatoid synovial tissue (ST) and FLS. RKIP overexpression significantly decreased IL-6 mRNA expression in TNF-alpha-stimulated rheumatoid FLS. RKIP overexpression also showed a decreased trend in IL-8, MMP-1, and MMP-3 mRNA expression in TNF-alpha-stimulated rheumatoid FLS. RKIP silencing resulted in significantly increased MMP-1 and MMP-3 mRNA expression in TNF-alpha-stimulated rheumatoid FLS. RKIP silencing also increased IL-6 and IL-8 mRNA expression in TNF-alpha-stimulated rheumatoid FLS, but this increase did not reach statistical significance. TNF-alpha-induced ERK and NF-kappa B activation was suppressed in FLS with RKIP overexpression. RKIP silencing resulted in a significantly higher invasion index in TNF-alpha-stimulated rheumatoid FLS compared to controls. These results suggest that RKIP might be a potential therapeutic target for rheumatoid arthritis.

引用

页码：474 / 483

页数：10

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