Interferon-gamma induces expression of interleukin-18 binding protein in fibroblast-like synoviocytes.
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.


CONCLUSIONS
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.
Möller
B
B
Rheumazentrum Rhein-Main/Medizinische Klinik III, Frankfurt am Main, Germany. b.moeller@em.uni-frankfurt.de
Paulukat
J
J
Nold
M
M
Behrens
M
M
Kukoc-Zivojnov
N
N
Kaltwasser
J P
JP
Pfeilschifter
J
J
Mühl
H
H
D001168:Arthritis / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025242:Spondylarthropathies / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C118370:interleukin-18 binding protein; D007371:Interferon-gamma