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The Role of Raf Kinase Inhibitor Protein in Rheumatoid Fibroblast-like Synoviocytes Invasiveness and Cytokine and Matrix Metalloproteinase Expression.
MedLine Citation:
PMID:  21556737     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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-κB 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-α-stimulated rheumatoid FLS. RKIP overexpression also showed a decreased trend in IL-8, MMP-1, and MMP-3 mRNA expression in TNF-α-stimulated rheumatoid FLS. RKIP silencing resulted in significantly increased MMP-1 and MMP-3 mRNA expression in TNF-α-stimulated rheumatoid FLS. RKIP silencing also increased IL-6 and IL-8 mRNA expression in TNF-α-stimulated rheumatoid FLS, but this increase did not reach statistical significance. TNF-α-induced ERK and NF-κB activation was suppressed in FLS with RKIP overexpression. RKIP silencing resulted in a significantly higher invasion index in TNF-α-stimulated rheumatoid FLS compared to controls. These results suggest that RKIP might be a potential therapeutic target for rheumatoid arthritis.
Authors:
Joong Kyong Ahn; Ji-Won Hwang; Eun-Kyung Bae; Jaejoon Lee; Chan Hong Jeon; Eun-Mi Koh; Hoon-Suk Cha
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-10
Journal Detail:
Title:  Inflammation     Volume:  -     ISSN:  1573-2576     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600105     Medline TA:  Inflammation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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