title: Smoking induces transcription of the heat shock protein system in the joints.
abstract: OBJECTIVE
  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.
authors.affiliation: Center of Experimental Rheumatology and Center of Integrative Human Physiology (ZIHP), University Hospital, Zurich, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ospelt
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Giovanni G
authors.initials: GG
authors.lastname: Camici
authors.affiliation: Center of Experimental Rheumatology and Center of Integrative Human Physiology (ZIHP), University Hospital, Zurich, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Engler
authors.affiliation: Schulthess Clinic, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kolling
authors.affiliation: Department of Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Vogetseder
authors.affiliation: Center of Experimental Rheumatology and Center of Integrative Human Physiology (ZIHP), University Hospital, Zurich, Switzerland.
authors.forename: Renate E
authors.initials: RE
authors.lastname: Gay
authors.affiliation: Center of Experimental Rheumatology and Center of Integrative Human Physiology (ZIHP), University Hospital, Zurich, Switzerland.
authors.forename: Beat A
authors.initials: BA
authors.lastname: Michel
authors.affiliation: Center of Experimental Rheumatology and Center of Integrative Human Physiology (ZIHP), University Hospital, Zurich, Switzerland.
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
mesh_terms: D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007596:Joints / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012906:Smoke; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism*; D014026:Nicotiana; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012906:Smoke
keywords: Fibroblasts; Rheumatoid Arthritis; Smoking