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Rheumatology Advance Access published online on January 29, 2008
Rheumatology, doi:10.1093/rheumatology/kem298
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

NF-{kappa}B and its relevance to arthritis and inflammation

R. E. Simmonds and B. M. Foxwell

Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London.

Correspondence to: B. M. Foxwell, Cytokine and Signal Transduction Laboratory, Kennedy Institute of Rheumatology, 1 Aspenlea Road, London W6 8LH, UK. E-mail: b.foxwell{at}imperial.ac.uk


  Abstract

In the synovial cells of patients with RA, activation of the nuclear factor-{kappa}B (NF-{kappa}B) pathway results in the transactivation of a multitude of responsive genes that contribute to the inflammatory phenotype, including TNF-{alpha} from macrophages, matrix metalloproteinases from synovial fibroblasts and chemokines that recruit immune cells to the inflamed pannus. This is largely a consequence of activation of the ‘canonical’ NF-{kappa}B pathway that involves heterodimers of p50/p65. Whilst much information on the role of NF-{kappa}B in inflammation has been gleaned from genetic deficiency of the respective genes in mice, important differences exist in the signalling networks between human and murine immune cells and immortalized cell lines. Despite these differences at the molecular level, the importance of NF-{kappa}B in inflammation is undisputed and inhibition of the pathway is widely believed to have great potential as a therapeutic target in RA. Commercial effort has gone into developing inhibitors of NF-{kappa}B activation. However, inhibition of the NF-{kappa}B activation can result in an exacerbation of inflammation if TNF-{alpha} production by macrophages is not controlled. It will be important that such inhibitors are carefully monitored before their long-term use in chronic inflammatory conditions such as RA.

KEY WORDS: NF-{kappa}B, Signalling pathways, Review

Submitted 13 July 2007; revised version accepted 4 October 2007.
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