Gliostatin as a clinical marker of rheumatoid arthritis and its regulation

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The objective was to assess the congruity of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) with other clinical markers of rheumatoid arthritis (RA) and to define its molecular mechanism of action in the complicated cytokine network during RA pathogenesis. Immunoassay systems were used to quantify GLS or cytokines levels in laboratory and clinical samples. The mean GLS concentration (S.E.M.) in synovial fluids of 38 samples from patient with RA was 384.5 (42.9)ng/ml. Its level (ng/ml) was two to three orders of magnitude higher than those of interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor alpha (TNFalpha) (pg/ml) which have been reported to have been a close relevance with RA etiology. The GLS levels in synovial fluid were correlated with IL-1 and IL-8, but not with TNFalpha and IL-6. There was no correlation The serial data of serum GLS levels well reflected changes in the disease activity during the clinical course of four representative patients with RA.In cultured fibroblast-like synoviocytes (FLS), TNFalpha, IL-1, IL-6, and IL-8 induced GLS expression. In particular, TNFalpha increased GLS production in a dose-dependent manner. The induction of GLS mRNA in FLSs by TNFalpha, IL-1, IL-6, and IL-8 was also examined by reverse transcription-polymerase chain reaction methods. In conclusion, our results suggest that serum GLS level mostly derived from cytokine-stimulated synoviocytes was a useful clinical marker of RA.