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KMID : 0388220100170020153
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Journal of the Korean Rheumatism Association
2010 Volume.17 No. 2 p.153 ~ p.161
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Peroxisome Proliferator-activated Receptor-? Agonist Inhibits Pro-inflammatory Gene Expressions and Cellular Proliferation of Fibroblast Like Synoviocytes from Patients with Rheumatoid Arthritis by Down-regulation of NF-kappaB
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Kwon Yong-Jin
Jung Soo-Jin
Kim Tae-Yeon
Park Min-Chan
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Abstract
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Objective: This study investigated the effect of rosiglitazone, a synthetic peroxisome proliferator- activated receptor-? (PPAR-?) 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 ?M, 50 ?M and 150 ?M rosiglitazone with or without TNF-? (10 ng/mL) stimulation. FLS proliferation in response to rosiglitazone treatment was measured by MTT assay, and mRNA expressions of IL-1?, 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-?B activation were evaluated using electrophoretic mobility shift assay (EMSA).
Results: Rosiglitazone treatment without TNF-? induced a dose-dependent reduction in mRNA expressions of IL-1?, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 from RA FLS. When TNF-? were treated with rosiglitazone, mRNA expressions of COX-2, MMP-9 were reduced dose- dependently. But mRNA expressions of IL-1?, IL-6, CCL-2, CCL-7 were increased in 10 ?M rosiglitazone with TNF-? 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-?B expression with rosiglitazone treatment.
Conclusion: Rosiglitazone suppressed cellular proliferation and mRNA expressions of pro-inflammatory mediators by down-regulating the NF-?B signaling pathway in RA FLS. The outcomes suggest that activation of PPAR-? can be a novel therapeutic approach in RA.
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KEYWORD
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Rosiglitazone, Rheumatoid arthritis, Fibroblast-like synoviocytes, Pro-inflammatory mediators, NF-?B
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