Original Article

The Journal of the Korean Rheumatism Association 2010; 17(2): 153-161

Published online June 30, 2010

© Korean College of Rheumatology

류마티스관절염 활막세포에서 Peroxisome Proliferator-activated Receptor-Ճ Agonist 처치의 염증매개인자 감소 및 활막세포 증식의 억제효과

권용진ㆍ정수진ㆍ김태연ㆍ박민찬

연세대학교 의과대학 내과학교실

Peroxisome Proliferator-activated Receptor-Ճ Agonist Inhibits Pro-inflammatory Gene Expressions and Cellular Proliferation of Fibroblast Like Synoviocytes from Patients with Rheumatoid Arthritis by Down-regulation of NF-kappaB

Yong-Jin Kwon, Soo-Jin Chung, Tae-Yeon Kim, Min-Chan Park

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

Correspondence to : Min-Chan Park

Abstract

Objective: This study investigated the effect of rosiglitazone, a synthetic peroxisome proliferator- activated receptor-Ճ (PPAR-Ճ) 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 ՌM, 50 ՌM and 150 ՌM rosiglitazone with or without TNF-Ձ (10 ng/mL) stimulation. FLS proliferation in response to rosiglitazone treatment was measured by MTT assay, and mRNA expressions of IL-1Ղ, 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-ՊB activation were evaluated using electrophoretic mobility shift assay (EMSA).
Results: Rosiglitazone treatment without TNF-Ձ induced a dose-dependent reduction in mRNA expressions of IL-1Ղ, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 from RA FLS. When TNF-Ձ were treated with rosiglitazone, mRNA expressions of COX-2, MMP-9 were reduced dose- dependently. But mRNA expressions of IL-1Ղ, IL-6, CCL-2, CCL-7 were increased in 10 ՌM rosiglitazone with TNF-Ձ 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-ՊB expression with rosiglitazone treatment.
Conclusion: Rosiglitazone suppressed cellular proliferation and mRNA expressions of pro-inflammatory mediators by down-regulating the NF-ՊB signaling pathway in RA FLS. The outcomes suggest that activation of PPAR-Ճ can be a novel therapeutic approach in RA.

Keywords Rosiglitazone, Rheumatoid arthritis, Fibroblast-like synoviocytes, Pro-inflammatory mediators, NF-ՊB

Article

Original Article

The Journal of the Korean Rheumatism Association 2010; 17(2): 153-161

Published online June 30, 2010

Copyright © Korean College of Rheumatology.

류마티스관절염 활막세포에서 Peroxisome Proliferator-activated Receptor-Ճ Agonist 처치의 염증매개인자 감소 및 활막세포 증식의 억제효과

권용진ㆍ정수진ㆍ김태연ㆍ박민찬

연세대학교 의과대학 내과학교실

Peroxisome Proliferator-activated Receptor-Ճ Agonist Inhibits Pro-inflammatory Gene Expressions and Cellular Proliferation of Fibroblast Like Synoviocytes from Patients with Rheumatoid Arthritis by Down-regulation of NF-kappaB

Yong-Jin Kwon, Soo-Jin Chung, Tae-Yeon Kim, Min-Chan Park

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

Correspondence to:Min-Chan Park

Abstract

Objective: This study investigated the effect of rosiglitazone, a synthetic peroxisome proliferator- activated receptor-Ճ (PPAR-Ճ) 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 ՌM, 50 ՌM and 150 ՌM rosiglitazone with or without TNF-Ձ (10 ng/mL) stimulation. FLS proliferation in response to rosiglitazone treatment was measured by MTT assay, and mRNA expressions of IL-1Ղ, 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-ՊB activation were evaluated using electrophoretic mobility shift assay (EMSA).
Results: Rosiglitazone treatment without TNF-Ձ induced a dose-dependent reduction in mRNA expressions of IL-1Ղ, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 from RA FLS. When TNF-Ձ were treated with rosiglitazone, mRNA expressions of COX-2, MMP-9 were reduced dose- dependently. But mRNA expressions of IL-1Ղ, IL-6, CCL-2, CCL-7 were increased in 10 ՌM rosiglitazone with TNF-Ձ 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-ՊB expression with rosiglitazone treatment.
Conclusion: Rosiglitazone suppressed cellular proliferation and mRNA expressions of pro-inflammatory mediators by down-regulating the NF-ՊB signaling pathway in RA FLS. The outcomes suggest that activation of PPAR-Ճ can be a novel therapeutic approach in RA.

Keywords: Rosiglitazone, Rheumatoid arthritis, Fibroblast-like synoviocytes, Pro-inflammatory mediators, NF-Պ,B

JRD
Jan 01, 2025 Vol.32 No.1, pp. 1~7
COVER PICTURE
Cumulative growth of rheumatology members and specialists (1980~2024). Cumulative distribution of the number of the (A) Korean College of Rheumatology members and (B) rheumatology specialists. (J Rheum Dis 2025;32:63-65)

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