Smoking induces transcription of the heat shock protein system in the joints

C Ospelt, GG Camici, A Engler, C Kolling… - Annals of the …, 2014 - ard.bmj.com
C Ospelt, GG Camici, A Engler, C Kolling, A Vogetseder, RE Gay, BA Michel, S Gay
Annals of the rheumatic diseases, 2014ard.bmj.com
Objectives Smoking increases the risk of developing rheumatoid arthritis (RA) and worsens
the course of the disease. In the current study we analysed whether smoking can affect gene
expression directly in the joints. Methods Synovial fibroblasts were incubated with 5%
cigarette smoke extract and changes in gene expression were detected using whole
genome microarrays and verified with real-time PCR. Synovial tissues were obtained from
smoking and non-smoking patients with RA undergoing joint replacement surgery and from …
Objectives
Smoking increases the risk of developing rheumatoid arthritis (RA) and worsens the course of the disease. In the current study we analysed whether smoking can affect gene expression directly in the joints.
Methods
Synovial fibroblasts were incubated with 5% cigarette smoke extract and changes in gene expression were detected using whole genome microarrays and verified with real-time PCR. Synovial tissues were obtained from smoking and non-smoking patients with RA undergoing joint replacement surgery and from mice exposed to cigarette smoke or ambient air in a whole body exposure chamber for 3 weeks.
Results
Microarray and real-time PCR analysis showed a significant upregulation of the heat shock proteins DnaJA4, DnaJB4, DnaJC6, HspB8 and Hsp70 after stimulation of synovial fibroblasts with 5% cigarette smoke extract. Similarly, in synovial tissues of smokers with RA the expression of DnaJB4, DnaJC6, HspB8 and Hsp70 was significantly higher compared with non-smokers with RA. Upregulation of DnaJB4 and DnaJC6 in joints by smoking was also confirmed in mice exposed to cigarette smoke.
Conclusions
Our data clearly show that smoking can change gene expression in the joints, which can lead to the activation of signalling pathways that promote development of autoimmunity and chronic joint inflammation.
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