Activation of Synovial Fibroblasts in Rheumatoid Arthritis

  • Steffen Gay1,

    Affiliated with

    • Thomas Pap1,

      Affiliated with

      • Michael Nawrath1,

        Affiliated with

        • Juliane K Franz1 and

          Affiliated with

          • Renate E Gay1

            Affiliated with

            Arthritis Res19991(Suppl 1):S19

            DOI: 10.1186/ar33

            Published: 15 November 1999

            Full text

            Activation of synovial fibroblasts (SF) by upregulation of proto-oncogenes is thought to play a major role in rheumatoid joint destruction. To explore distinct signaling pathways in this activation we used retroviral gene transfer in the SCID mouse model. Specifically, we transferred dominant negative (dn) mutants, such as dn Raf-1 and dn c-myc to inhibit the Ras-Raf-MAPK cascade as well as the cascade involving myc. FLAG-tagged constructs used in this study were cloned into the retroviral vector LXSN. The data show that both Raf- as well as myc-dependent pathways contribute to the activation of synovial fibroblasts in RA.

            Since mutations in PTEN have been described in cancer and associated with their invasiveness we studied the expression of this novel tumor-suppressor in RA. Although, no mutations of PTEN could be detected in RA synovium, only 40% of cultured RA-SF expressed PTEN, and a down-regulation was observed at sites of invasion into cartilage. These findings suggest that endogenous or autocrine down-regulation of this tumor-suppressor may contribute to the invasive behavior of RA-SF by maintaining their aggressive phenotype at sites of cartilage destruction in RA. Most interestingly, the same SF found at these sites are also the major producers of interleukin-16, a strong chemoattractant for CD4+ cells.

            Authors’ Affiliations

            (1)
            University Hospital

            References

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            Copyright

            © Current Science Ltd 2000

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