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Smoking induces transcription of the heat shock protein system in the joints
  1. Caroline Ospelt1,
  2. Giovanni G Camici2,
  3. Anna Engler1,
  4. Christoph Kolling3,
  5. Alexander Vogetseder4,
  6. Renate E Gay1,
  7. Beat A Michel1,
  8. Steffen Gay1
  1. 1Center of Experimental Rheumatology and Center of Integrative Human Physiology (ZIHP), University Hospital, Zurich, Switzerland
  2. 2Institute of Physiology, University of Zurich, Zurich, Switzerland
  3. 3Schulthess Clinic, Zurich, Switzerland
  4. 4Department of Pathology, University Hospital Zurich, Zurich, Switzerland
  1. Correspondence to Dr Caroline Ospelt, Center of Experimental Rheumatology, University Hospital Zurich, Gloriastrasse 23, Zurich CH-8091, Switzerland; caroline.ospelt{at}usz.ch

Abstract

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.

  • Fibroblasts
  • Rheumatoid Arthritis
  • Smoking

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