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Inflammation Research

, 60:1021 | Cite as

Fibrinolysis is down-regulated in mouse collagen-induced arthritis, but its normalization does not alleviate the course of disease

  • Jakub KwiecińskiEmail author
  • Elisabet Josefsson
  • Tao Jin
Original Research Paper

Abstract

Objective

Down-regulation of fibrinolysis and increased fibrin deposition in joints are hallmarks of rheumatoid arthritis (RA), and are believed to be involved in disease progression. The mouse model of collagen-induced arthritis (CIA) closely resembles RA and has been used to explore mechanism and treatments of RA, but neither the fibrinolytic system nor pro-fibrinolytic therapies were investigated in CIA.

Materials and methods

Plasmin activity, levels of plasminogen activator inhibitor (PAI-1), D-dimer, and IL-6 were measured in plasma of CIA mice. Fibrin deposition and PAI-1 levels were also measured in inflamed joints. Mice were treated with plasminogen activators uPA (urokinase-type plasminogen activator) or tPA (tissue-type plasminogen activator). Effects of treatment on disease severity and fibrinolytic system were assessed.

Results

CIA caused decrease in plasmin activity, accompanied by increase in PAI-1 levels, in both blood and inflamed joints. This resulted in massive fibrin deposition in synovium. PAI-1 levels correlated negatively with plasmin activity and positively with IL-6. Treatments with uPA and tPA improved plasmin activity and removed fibrin deposits in inflamed joints. However, disease severity remained unchanged.

Conclusions

Fibrinolytic changes in CIA parallel changes in RA, making CIA a suitable model to study fibrinolysis in RA. Normalization of plasmin activity in CIA after treatment with plasminogen activators had no effect on disease severity.

Keywords

Rheumatoid arthritis Collagen-induced arthritis Fibrinolysis Plasmin tPA uPA 

Notes

Acknowledgments

Authors are grateful to Malin Erlandsson and Ing-Marie Jonsson for their excellent technical assistance and to Maria Bokarewa for critical reading of the manuscript. This work was supported by Göteborg Medical Society, King Gustaf V:s Foundation, Åke Wiberg’s Foundation, Nanna Svartz’ Foundation, Rune and Ulla Amlöv’s Foundation, Swedish Rheumatism Association, Göteborg Rheumatism Association, The family Thölens and Kristlers Foundation, Tore Nilsson’s Foundation, and the University of Göteborg.

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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • Jakub Kwieciński
    • 1
    Email author
  • Elisabet Josefsson
    • 1
  • Tao Jin
    • 1
  1. 1.Department of Rheumatology and Inflammation Research, Institute of Medicine at Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden

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