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Basic and translational research
Extended report
The impact of endogenous annexin A1 on glucocorticoid control of inflammatory arthritis
  1. Hetal B Patel1,
  2. Kristin N Kornerup1,
  3. Andre' LF Sampaio1,
  4. Fulvio D'Acquisto1,
  5. Michael P Seed1,
  6. Ana Paula Girol2,
  7. Mohini Gray3,
  8. Costantino Pitzalis1,
  9. Sonia M Oliani2,
  10. Mauro Perretti1
  1. 1William Harvey Research Institute, Barts and The London School of Medicine, London UK
  2. 2Department of Biology; Instituto de Biociências, Letras e Ciências Exatas (IBILCE), São Paulo State University, São José do Rio Preto, Brazil
  3. 3Medical Research Council Centre for Inflammation, University of Edinburgh, Edinburgh, UK Experimental Medicine and Rheumatology, William Harvey Research Institute, London, UK
  1. Correspondence to Mauro Perretti, Barts and The London School of Medicine, William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UK; m.perretti{at}qmul.ac.uk

Abstract

Objectives To establish the role and effect of glucocorticoids and the endogenous annexin A1 (AnxA1) pathway in inflammatory arthritis.

Methods Ankle joint mRNA and protein expression of AnxA1 and its receptors were analysed in naive and arthritic mice by real-time PCR and immunohistochemistry. Inflammatory arthritis was induced with the K/BxN arthritogenic serum in AnxA1+/+ and AnxA1−/− mice; in some experiments, animals were treated with dexamethasone (Dex) or with human recombinant AnxA1 or a protease-resistant mutant (termed SuperAnxA1). Readouts were arthritic score, disease incidence, paw oedema and histopathology, together with pro-inflammatory gene expression.

Results All elements of the AnxA1 pathway could be detected in naive joints, with augmentation during ongoing disease, due to the infiltration of immune cells. No difference in arthritis intensity of profile could be observed between AnxA1+/+ and AnxA1−/− mice. Treatment of mice with Dex (10 µg intraperitoneally daily from day 2) afforded potent antiarthritic effects highly attenuated in the knockouts: macroscopic changes were mirrored by histopathological findings and pro-inflammatory gene (eg, Nos2) expression. Presence of proteinase 3 mRNA in the arthritic joints led the authors to test AnxA1 and the mutant SuperAnxA1 (1 µg intraperitoneally daily in both cases from day 2), with the latter one being able to accelerate the resolving phase of the disease.

Conclusion AnxA1 is an endogenous determinant for the therapeutic efficacy of Dex in inflammatory arthritis. Such an effect can be partially mimicked by application of SuperAnxA1 which may represent the starting point for novel antiarthritic therapeutic strategies.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ and http://creativecommons.org/licenses/by-nc/3.0/legalcode

https://doi.org/10.1136/annrheumdis-2011-201180

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    Footnotes

    • Funding This work was supported by a Wellcome Trust (UK) project grant 083551. SMO is funded by Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (Grant 2011/00128-1) and Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (Grant 302768/2010-6).

    • Competing interests None.

    • Provenance and peer review Not commissioned; externally peer reviewed.