Gliostatin as a clinical marker of rheumatoid arthritis and its regulation

目的是评估胶质抑制素/血小板衍生内皮细胞生长因子（GLS/PD-ECGF）与类风湿关节炎（RA）的其他临床标志物的一致性，并确定其在RA发病过程中复杂的细胞因子网络中的分子作用机制。免疫测定系统用于定量实验室和临床样品中的GLS或细胞因子水平。38例RA患者滑液GLS平均浓度（S.E.M.）为384.5 (42.9)ng/ml。其水平（ng/ml）比白细胞介素-1 （IL-1）、IL-6、IL-8和肿瘤坏死因子α (TNFalpha) （pg/ml）高2 - 3个数量级，据报道与RA病因密切相关。滑液GLS水平与IL-1、IL-8相关，与TNFalpha、IL-6无关。血清GLS水平的序列数据很好地反映了4例具有代表性的RA患者临床病程中疾病活动度的变化。在培养的成纤维细胞样滑膜细胞（FLS）中，TNFalpha、IL-1、IL-6和IL-8诱导GLS表达。特别是，TNFalpha以剂量依赖的方式增加GLS的产生。通过逆转录-聚合酶链反应方法检测TNFalpha、IL-1、IL-6和IL-8对FLSs中GLS mRNA的诱导作用。总之，我们的结果表明血清GLS水平主要来源于细胞因子刺激的滑膜细胞，是RA的一个有用的临床标志物。

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.