Induction of CCL13 expression in synovial fibroblasts underlines a significant role of oncostatin M in rheumatoid arthritis

  • C Hintzen
  • S Quaiser
  • T Pap
  • PC Heinrich
  • HM Hermanns
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Keywords

Rheumatoid Arthritis Rheumatoid Arthritis Patient Synovial Fluid Synovial Fibroblast Joint Destruction 

Rheumatoid arthritis (RA) is a severe, chronic disease characterized by a profound inflammatory response that leads to both joint destruction as well as extraarticular symptoms with a significant impact on both morbidity and mortality. The cause and pathologic process underlying RA have not yet been fully elucidated. However, it is clear that both the cellular immune system and the cytokine network are subject to profound dysregulations. The success of an anti-proinflammatory cytokine therapy directed against either tumor necrosis factor alpha (TNFα) or, to a lesser extent, interleukin-1 (IL-1), has highlighted the significance of these cytokines in the pathological progession of RA. Nevertheless, these therapeutical strategies are not beneficial to all patients, suggesting that other cytokines like IL-6, oncostatin M, IL-4, IL-13, IFNγ are also present in the synovial fluid of chronically inflamed joints. Here we demonstrate that among a number of cytokines present in the synovial fluid of RA patients, only OSM induces a prolonged expression of the chemokine CCL13. The expression of CCL13 appears to be tissue-specific since neither in dermal nor lung or cervix fibroblasts CCL13 expression could be observed. We identify human synovial fibroblasts (HSF) as well as synovial fibroblasts of RA patients (RASFs) as producers of CCL13. The expression of CCL13 is mediated through STAT5 activation and p38 MAPK-dependent pathways and results in increased migration of monocytic cells.

Copyright information

© Hintzen et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

Authors and Affiliations

  • C Hintzen
    • 1
  • S Quaiser
    • 2
  • T Pap
    • 3
  • PC Heinrich
    • 4
  • HM Hermanns
    • 1
  1. 1.Rudolf-Virchow-CenterUniversity of WürzburgWürzburgGermany
  2. 2.Department of BiochemistryUniversity Hospital RWTHAachenGermany
  3. 3.Division of Molecular Medicine of Musculoskeletal Tissue, Department of OrthopedicsUniversity of MünsterMünsterGermany
  4. 4.Department of Biochemistry and Molecular BiologyUniversity of FreiburgFreiburgGermany

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