Peroxisome Proliferator-activated Receptor-gamma Agonist Inhibits Pro-inflammatory Gene Expressions and Cellular Proliferation of Fibroblast Like Synoviocytes from Patients with Rheumatoid Arthritis by Down-regulation of NF-kappaB.
10.4078/jkra.2010.17.2.153
- Author:
Yong Jin KWON
1
;
Soo Jin CHUNG
;
Tae Yeon KIM
;
Min Chan PARK
Author Information
1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. mcpark@yuhs.ac
- Publication Type:Original Article
- Keywords:
Rosiglitazone;
Rheumatoid arthritis;
Fibroblast-like synoviocytes;
Pro-inflammatory mediators;
NF-kappaB
- MeSH:
Arthritis, Rheumatoid;
Arthroplasty, Replacement, Knee;
Cell Proliferation;
Down-Regulation;
Electrophoretic Mobility Shift Assay;
Fibroblasts;
Gene Expression;
Humans;
Interleukin-6;
NF-kappa B;
Peroxisomes;
RNA, Messenger;
Thiazolidinediones;
Tumor Necrosis Factor-alpha
- From:The Journal of the Korean Rheumatism Association
2010;17(2):153-161
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVE: This study investigated the effect of rosiglitazone, a synthetic peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, on pro-inflammatory gene expressions and cellular proliferation of fibroblast like synoviocyte (FLS) from patients with rheumatoid arthritis (RA), and to determine whether these actions are mediated by nuclear factor-kappaB (NF-B) down-regulation. METHODS: Synovial tissues from patients with RA were obtained during total knee replacement surgery, and FLS were isolated. RA FLS were subsequently treated with 10 micrometer, 50 micrometer and 150 micrometer rosiglitazone with or without TNF-alpha (10 ng/mL) stimulation. FLS proliferation in response to rosiglitazone treatment was measured by MTT assay, and mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 were determined by real-time quantitative RT-PCR. The effects of rosiglitazone on NF-kappaB activation were evaluated using electrophoretic mobility shift assay (EMSA). RESULTS: Rosiglitazone treatment without TNF-alpha induced a dose-dependent reduction in mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 from RA FLS. When TNF-alpha were treated with rosiglitazone, mRNA expressions of COX-2, MMP-9 were reduced dose-dependently. But mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7 were increased in 10 micrometer rosiglitazone with TNF-alpha and then decreased as the concentration of rosiglitazone increased. Rosiglitazone treatment also suppressed FLS proliferation in a dose-dependent manner, and EMSA showed decreased NF-kappaB expression with rosiglitazone treatment. CONCLUSION: Rosiglitazone suppressed cellular proliferation and mRNA expressions of pro-inflammatory mediators by down-regulating the NF-kappaB signaling pathway in RA FLS. The outcomes suggest that activation of PPAR-gamma can be a novel therapeutic approach in RA.
