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Interferon-gamma induces expression of interleukin-18 binding protein in fibroblast-like synoviocytes
1Rheumazentrum Rhein-Main/Medizinische Klinik III, Frankfurt am Main, Germany. b.moeller@em.uni-frankfurt.de
Objective:
To investigate expression of the endogenous antagonist of interleukin 18 (IL-18) bioactivity, IL-18 binding protein isoform a (IL-18BPa), in fibroblast-like synoviocytes (FLS).
Methods:
Long-term cultured FLS from rheumatoid arthritis (RA), osteoarthritis (OA) and spondylarthropathy patients were analysed for spontaneous and cytokine-induced IL-18BPa expression. Messenger RNA and release of IL-18BPa were assessed by semi-quantitative and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) as well as immunoblot analysis, respectively.
Results:
All investigated FLS cultures expressed low amounts of IL-18BPa transcripts. However, there was no detectable release of IL-18BPa from unstimulated synoviocytes. Of the investigated cytokines, only interferon (IFN)-gamma markedly up-regulated IL-18BPa mRNA levels. Induction was accompanied by release of IL-18BPa immunoreactivity from FLS. Conditioned media from IFN-gamma-stimulated FLS cultures reduced IL-12/IL-18-dependent IFN- production by peripheral blood mononuclear cells.
Conclusion:
The present data imply that IFN--activated synoviocytes mediate a negative feedback loop via IL-18BPa, which may limit IL-18 biological activity in arthritis.