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

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.

journal_name

Ann Rheum Dis

authors

Ospelt C,Camici GG,Engler A,Kolling C,Vogetseder A,Gay RE,Michel BA,Gay S

doi

10.1136/annrheumdis-2013-204486

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

1423-6

issue

7

eissn

0003-4967

issn

1468-2060

pii

annrheumdis-2013-204486

journal_volume

73

pub_type

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