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Open Access Research article

IL-17-mediated Bcl-2 expression regulates survival of fibroblast-like synoviocytes in rheumatoid arthritis through STAT3 activation

Seon-Yeong Lee1, Seung-Ki Kwok12, Hye-Jin Son1, Jun-Geol Ryu1, Eun-Kyung Kim1, Hye-Jwa Oh1, Mi-La Cho1*, Ji Hyeon Ju12, Sung-Hwan Park12 and Ho-Youn Kim12

Author affiliations

1 The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea

2 Center for Rheumatic Disease, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea

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Citation and License

Arthritis Research & Therapy 2013, 15:R31  doi:10.1186/ar4179

Published: 20 February 2013

Abstract

Introduction

Fibroblast-like synoviocytes (FLSs) are a major cell population of the pannus that invades adjacent cartilage and bone in rheumatoid arthritis (RA). The study was undertaken to determine the effect of interleukin-17 (IL-17) on the survival and/or proliferation of FLSs from RA patients and to investigate whether signal tranducer and activator of transcription 3 (STAT3) is implicated in this process.

Methods

Bcl-2 and Bax expression in FLSs was determined using the real-time PCR and western blot analysis. The expression of Bcl-2 and phosphoSTAT3 in synovial tissues was investigated by confocal microscope. Apoptosis of FLSs was detected by Annexin V/propidium iodide staining and/or phase contrast microscopy. The proliferation of FLSs was determined by CCK-8 ELISA assay.

Results

The pro-apoptotic Bax is decreased and anti-apoptotic Bcl-2 is increased in FLSs from RA patients compared with those from patients with osteoarthritis (OA). IL-17 upregulated the expression of Bcl-2 in FLSs from RA patients, but not in FLSs from OA patients. STAT3 was found to mediate IL-17-induced Bcl-2 upregulation in FLSs from RA patients. Additionally, IL-17 promoted the survival and proliferation of FLSs from RA patients. Most importantly, treatment with STAT3 inhibitor reversed the protective effect of IL-17 on FLSs apoptosis induced by sodium nitroprusside (SNP).

Conclusions

Our data demonstrate that STAT3 is critical in IL-17-induced survival of FLS from RA patients. Therefore, therapeutic strategies that target the IL-17/STAT3 pathway might be strong candidates for RA treatment modalities.