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Inhibition of glycogen synthase kinase-3β suppresses inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes and collagen-induced arthritis.

Authors
 Yong-Jin Kwon  ;  Chong-Hyeon Yoon  ;  Sang-Won Lee  ;  Yong-Beom Park  ;  Soo-Kon Lee  ;  Min-Chan Park 
Citation
 Joint Bone Spine, Vol.81(3) : 240-246, 2014 
Journal Title
 Joint Bone Spine 
ISSN
 1297-319X 
Issue Date
2014
Abstract
OBJECTIVES: Glycogen synthase kinase (GSK)-3β, a serine/threonine protein kinase, has been implicated as a regulator of the inflammatory response. This study was performed to evaluate the effect of selective GSK-3β inhibitors in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and collagen-induced arthritis (CIA). METHOD: FLS from RA patients were treated with selective GSK-3β inhibitors, including lithium chloride, 6-bromoindirubin-3'-oxime (BIO), or 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8). The effects of GSK-3β inhibition on pro-inflammatory mediators were determined by real-time PCR and ELISA. The levels of NF-κB, phosphorylated JNK, c-jun, ATF-2 and p-38 proteins were evaluated by western blot analysis. The in vivo effects of GSK-3β inhibitors were examined in mice with CIA. RESULTS: Treatment of RA FLS with GSK-3β inhibitors induced dose-dependent reductions in gene expression and the production of pro-inflammatory mediators. The levels of NF-κB, phosphorylated JNK, c-jun, ATF-2 and p-38 were decreased following treatment with GSK-3β inhibitors. GSK-3β inhibitors treatment attenuated clinical and histological severities of CIA in mice. Infiltration of T-cells, macrophages, and tartrate-resistant acid phosphatase positive cells was decreased in joint sections of CIA mice by GSK-3β inhibitors treatment. Serum levels of IL-1β, IL-6, TNF-α and IFN-γ in CIA mice were also significantly decreased in dose-dependent manners by treatment with GSK-3β inhibitors. CONCLUSION: Treatment with GSK-3β inhibitors suppressed inflammatory responses in RA FLS and CIA mice. These findings suggest that the inhibition of GSK-3β can be used as an effective therapeutic agent for RA.
Full Text
http://www.sciencedirect.com/science/article/pii/S1297319X13002157
DOI
10.1016/j.jbspin.2013.09.006
Appears in Collections:
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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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98769
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