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Arthritis Res Ther. 2012; 14(Suppl 1): P11.
Published online Feb 9, 2012. doi:  10.1186/ar3612
PMCID: PMC3332510
Cigarette smoke downregulates HDAC2 in rheumatoid arthritis synovial fibroblasts
Anna Engler,corresponding author1 Astrid Jüngel,1 Christoph Kolling,2 Beat A Michel,1 Renate Gay,1 Steffen Gay,1 and Caroline Ospelt1
1Center of Experimental Rheumatology, University Hospital Zurich and Zurich Center of Integrative Human Physiology (ZIHP), Zurich, Switzerland
2Schulthess Clinic, Zurich, Switzerland
corresponding authorCorresponding author.
Supplement
Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)
1478-6354-14-S1.pdf
Conference
8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)
14-16 November 2011
Tokyo, Japan
Background
Cigarette smoking has been shown as major environmental risk factor for rheumatoid arthritis (RA). Epidemiological studies indicate an association of cigarette smoking with development of RA [1,2], although molecular mechanisms remain unknown. The aim of this study is to analyze the influence of cigarette smoke on the gene expression regulated by histone deacetylases (HDACs) in RA synovial fibroblasts (RASF).
Methods
RASF obtained from patients undergoing joint replacement surgery were stimulated with freshly prepared cigarette smoke extract (CSE) for 24 hours. Expression of HDACs was measured at the mRNA level by Real-time TaqMan and SYBR green PCR and at the protein level by immunoblot analysis. Global histone 3 (H3) acetylation was analyzed by immunoblot.
Results
Stimulation of RASF (n = 8-10) with CSE significantly enhanced the expression of HDAC1 (x-fold: 2.0 ± 0.4; p = 0.04), HDAC2 (1.9 ± 0.3; p = 0.02) and HDAC3 (2.4 ± 0.4; p = 0.01) at the mRNA level while the expression of HDAC 4-11 remained unchanged. On the protein level, expression of HDAC1 and HDAC3 were not altered, whereas the expression of HDAC2 protein was decreased in CSE stimulated RASF. No measurable changes in global acetylation of H3 were induced by CSE in RASF (n = 6).
Conclusion
CSE specifically downregulates the expression of HDAC2 in RASF. Differential regulation of HDAC2 at the mRNA and protein level points to post-transcriptional degradation mechanisms induced by smoking. Even though global H3 acetylation was not changed by CSE, decreased HDAC2 levels might be associated with hyper-acetylation and thus increased expression of specific HDAC2 regulated genes.
References
  • Bergstrom U, Jacobsson LT, Nilsson JA, Berglund G, Turesson C. Pulmonary dysfunction, smoking, socioeconomic status and the risk of developing rheumatoid arthritis. Rheumatology (Oxford) 2011;50:2005–2013. doi: 10.1093/rheumatology/ker258. [PubMed] [Cross Ref]
  • Hutchinson D, Shepstone L, Moots R, Lear JT, Lynch MP. Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA. Ann Rheum Dis. 2001;60:223–227. doi: 10.1136/ard.60.3.223. [PMC free article] [PubMed] [Cross Ref]
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