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Joint Bone Spine
Volume 80, n° 6
pages 621-625 (décembre 2013)
Doi : 10.1016/j.jbspin.2013.02.009
accepted : 10 February 2013
A role for benzo[a]pyrene and Slug in invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis: A potential molecular link between smoking and radiographic progression

Jaejoon Lee a , Hyemin Jeong a, Eun-Jung Park a, Ji Won Hwang a, Eun-Kyung Bae b, Joong Kyong Ahn c, Kwang-Sung Ahn d, Eun-Mi Koh a, Hoon-Suk Cha a,
a Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 135-710, Republic of Korea 
b Samsung Biomedical Research Institute, 81 Irwon-Ro, Gangnam-Gu, Seoul, 135-710, Republic of Korea 
c Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108 Pyoung-Dong, Jongro-Gu, Seoul 110-746, Republic of Korea 
d Clinical Research Institute, Seoul National University Hospital, 28 yeongun-Dong, Jongro-Gu, Seoul 110-768, Republic of Korea 

Corresponding author. Tel.: +82 2 3410 3435; fax: +82 2 3410 3849.

To investigate the effects of benzo[a]pyrene (B[a]P), a major toxic component of cigarette smoke, on the expression of Slug and to determine the effect of B[a]P/Slug on the invasive properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS).


The expression of Slug was measured by real-time PCR following the stimulation of FLS with different concentrations of B[a]P or EGF. The phosphorylation of the key enzymes in the signaling pathway was analyzed by western blots. Inhibitors of PI3K/Akt/mTOR pathway were used to confirm the critical pathway for Slug expression. An in vitro cell invasion assay was performed using RA FLS treated with Slug cDNA, Slug small interference RNA, or control.


Slug expression increased significantly following treatment with B[a]P or EGF in a dose-dependent manner. The stimulation of FLS with B[a]P or EGF induced the phosphorylation of Akt kinase, but not in ERK, JNK and p38. The Slug mRNA expression induced by B[a]P and EGF decreased significantly following the treatment with PI3K/Akt/mTOR inhibitors. Slug overexpression using Slug cDNA upregulated the invasive function of FLS, and Slug depletion using siRNA showed the opposite effect compared with the control. In addition, the stimulation with B[a]P increased the invasive function of the control siRNA-treated FLS but not in the Slug siRNA-treated FLS.


Our data showed that B[a]P regulates the invasive properties of RA FLS through Slug expression. This mechanism may provide a novel molecular link underlying the association between smoking and increased radiographic progression in RA.

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Keywords : Rheumatoid Arthritis, Synoviocytes, Tobacco, Joint erosions, Risk factors

© 2013  Société française de rhumatologie@@#104156@@