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Inflammation Research

, Volume 55, Issue 10, pp 446–455 | Cite as

Taurine chloramine inhibits proliferation of rheumatoid arthritis synoviocytes by triggering a p53-dependent pathway

  • E. Kontny
  • W. Rudnicka
  • M. Chorąży-Massalska
  • J. Marcinkiewicz
  • W. Maśliński
Original Paper

Abstract.

Objective and Design

Taurine chloramine (Tau-Cl), originating from activated neutrophils, possesses antiinflammatory activities. Fibroblast-like synoviocytes (FLS) participate in the chronic synovitis and synovial membrane hyperplasia that are characteristic pathological features of rheumatoid arthritis (RA). The present study was conducted to investigate the mechanism of the Tau-Cl effect on the proliferation of these cells in culture.

Materials and methods

FLS were stimulated in vitro with platelet derived growth factor (PDGF) alone or together with Tau-Cl. Cell proliferation was evaluated by counting the total and dividing cell numbers and by measurement of 3H-thymidine incorporation. Expression of the key cell-cycle regulators was evaluated at the protein (Western blotting) and/or mRNA (RT-PCR) levels.

Results

Treatment of RA FLS with Tau-Cl (200–500 μM) resulted in an early nuclear accumulation of p53 tumor suppressor protein. Moreover, Tau-Cl inhibited PDGF-triggered cell proliferation (IC50 value ≈ 250–300 μM), accompanied by characteristic modulation of p53 transcriptional targets: down-regulation of proliferating cell nuclear antigen (PCNA) and survivin, and concomitant up-regulation of p21 mitotic inhibitor.

Conclusion

We propose that Tau-Cl inhibits proliferation of RA FLS by triggering a p53-dependent cell-cycle arrest and conclude that this compound suppresses pathways in FLS that are known to contribute to the pathology of RA.

Key words.

Taurine chloramine p53 tumor suppressor inflammation rheumatoid arthritis synoviocytes 

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Copyright information

© Birkhäuser Verlag, Basel 2006

Authors and Affiliations

  • E. Kontny
    • 1
  • W. Rudnicka
    • 1
  • M. Chorąży-Massalska
    • 1
  • J. Marcinkiewicz
    • 2
  • W. Maśliński
    • 1
  1. 1.Department of Pathophysiology and ImmunologyInstitute of RheumatologyWarsawPoland
  2. 2.Department of ImmunologyJagiellonian University Medical CollegeCracowPoland

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