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Secreted frizzled-related protein 5 suppresses inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes through down-regulation of c-Jun N-terminal kinase

 Yong-Jin Kwon  ;  Sang-Won Lee  ;  Yong-Beom Park  ;  Soo-Kon Lee  ;  Min-Chan Park 
 RHEUMATOLOGY , Vol.53(9) : 1704-1711, 2014 
Journal Title
Issue Date
Aged ; Arthritis, Rheumatoid/metabolism* ; Arthritis, Rheumatoid/pathology ; Cells, Cultured ; Down-Regulation/genetics ; Eye Proteins/biosynthesis ; Eye Proteins/genetics ; Eye Proteins/physiology* ; Female ; Fibroblasts/metabolism ; Gene Expression Regulation, Enzymologic/physiology ; Humans ; Inflammation Mediators/metabolism ; JNK Mitogen-Activated Protein Kinases/biosynthesis* ; Leukocytes, Mononuclear/metabolism ; MAP Kinase Signaling System/physiology ; Male ; Membrane Proteins/biosynthesis ; Membrane Proteins/genetics ; Membrane Proteins/physiology* ; Middle Aged ; Osteoarthritis, Knee/metabolism ; Osteoarthritis, Knee/pathology ; RNA Interference ; RNA, Messenger/genetics ; Synovial Membrane/metabolism* ; Synovial Membrane/pathology
Wnt signalling ; c-Jun N-terminal kinase ; fibroblast-like synoviocytes ; rheumatoid arthritis ; secreted frizzled-related protein 5
OBJECTIVE: This study was performed to investigate the effect of secreted frizzled-related protein 5 (Sfrp5), a novel anti-inflammatory adipokine that competes with the frizzled proteins for Wnt binding, on inflammatory response and the c-Jun N-terminal kinase (JNK) signalling pathway in RA. METHODS:Expression of Sfrp5 mRNA in peripheral blood mononuclear cells (PBMCs) and fibroblast-like synoviocytes (FLSs) from patients with RA and OA was determined using real-time quantitative PCR (qPCR). Sfrp5 RNA interference (RNAi) plasmids were transfected to abrogate Sfrp5 expression in RA FLSs, and adenovirus containing the Sfrp5 transcript was delivered into RA FLSs to strengthen Sfrp5 expression. Levels of pro-inflammatory genes and their protein products were determined using real-time qPCR and ELISA in RA FLSs. Production of mitogen-activated protein kinase kinase 7 (MKK-7), JNK and c-Jun were assessed by Western blot analysis. RESULTS:Expression of Sfrp5 mRNA was decreased in PMBCs and FLSs from patients with RA compared with patients with OA. Gene expression and production of IL-1β, IL-6, chemokine ligand 2 (CCL-2), CCL-7, cyclooxygenase 2 and MMP-9 were markedly increased in Sfrp5 RNAi plasmid-transfected RA FLSs, while transfection with adenoviral vectors encoding Sfrp5 induced reductions in those levels. Phosphorylated forms of MKK-7, JNK and c-Jun were increased by Sfrp5 RNAi plasmids and were decreased by adenoviral vectors encoding Sfrp5. CONCLUSION:Sfrp5 suppressed the inflammatory response and down-regulated JNK signalling in RA FLSs. These findings provide evidence for the anti-inflammatory effect of Sfrp5 in RA.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Yong Jin(권용진)
Park, Min Chan(박민찬) ORCID logo https://orcid.org/0000-0003-1189-7637
Park, Yong Beom(박용범)
Lee, Sang Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
Lee, Soo Kon(이수곤)
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