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This article is part of the supplement: 25th European Workshop for Rheumatology Research

Oral presentation

Chaperonins and the regulation of immunity

GS Panayi and VC Corrigall

Author Affiliations

Academic Department of Rheumatology, King's College London, Guy's Hospital, London, UK

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Arthritis Research & Therapy 2005, 7(Suppl 1):S2  doi:10.1186/ar1507


The electronic version of this article is the complete one and can be found online at:


Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Oral presentation

Chaperonins have classically been thought of as intracellular molecules involved in the correct folding of proteins. Their expression is upregulated during times of stress such as heat (hence their common nomenclature as heat shock proteins [HSP]), anoxia, hypoglycaemia and reactive oxygen species [1]. These are conditions found in infected tissues or in tissues with chronic inflammation such as the rheumatoid synovium. In their intracellular location they protect the cell from apoptotic death due to stress. Increasingly chaperonins have been recognised to subserve extracellular functions for which they have received the name 'chaperokines' since they bind to specific receptors on the cell surface and activate cells of the innate immune system to secrete inflammatory cytokines, chemokines and small molecular weight mediators such as prostaglandins [2]. Indeed, an early event in inflammation is cell stress/necrosis leading to the release of HSP60 and HSP70 that binds via a CD14-mediated mechanism to Toll-like receptors 2 and 4 [2] as part of the 'danger' signal [3]. The secretion of tumour necrosis factor alpha, IL-1, IL-12 and other chemokines prepares the environment for a TH1 adaptive immune response. It is now recognised that some chaperonins, such as BiP and HSP27, may activate the innate immune system to secrete anti-inflammatory cytokines, such as IL-10 [4,5] that may skew the adaptive immune response to TH2. Recent work by our group has shown that BiP can not only prevent but also treat ongoing collagen-induced arthritis in DBA/1 mice [6], suggesting that chaperonins may down modulate ongoing TH1 responses. Thus, it may be possible to suppress rheumatoid inflammation by administration of appropriate chaperonins such as BiP. Finally, chaperonins may be important system regulators determining the outcome between TH1 and Th2 immune responses.

Acknowledgements

GSP and VCC are shareholders in Immune Regulation Ltd that is investigating the potential of BiP as an immunotherapeutic agent for the treatment of rheumatoid arthritis.

References

  1. Pockley AG: Heat shock proteins as regulators of the immune response.

    Lancet 2003, 362:469-476. PubMed Abstract | Publisher Full Text OpenURL

  2. Asea A: Chaperokine-induced signal transduction pathways.

    Exerc Immunol Rev 2003, 9:25-33. PubMed Abstract OpenURL

  3. Matzinger P: The danger model: a renewed sense of self.

    Science 2002, 296:301-305. PubMed Abstract | Publisher Full Text OpenURL

  4. De AK, Kodys KM, Yeh BS, Miller-Graziano C: Exaggerated human monocyte IL-10 concomitant to minimal TNF-alpha induction by heat-shock protein 27 (Hsp27) suggests Hsp27 is primarily an antiinflammatory stimulus.

    J Immunol 2000, 165:3951-3958. PubMed Abstract | Publisher Full Text OpenURL

  5. Corrigall VM, Bodman-Smith MD, Brunst M, Cornell H, Panayi GS: Inhibition of antigen-presenting cell function and stimulation of human peripheral blood mononuclear cells to express an antiinflammatory cytokine profile by the stress protein BiP: relevance to the treatment of inflammatory arthritis.

    Arthritis Rheum 2004, 50:1164-1171. PubMed Abstract | Publisher Full Text OpenURL

  6. Panayi G, Brownlie R, Corrigall V, Bodman-Smith M, Thompson S: Immunotherapy of collagen induced arthritis with the stress protein BiP.

    FASEB J 2004, 18(suppl S):A1174. OpenURL