Interleukin-6 and oncostatin M are elevated in liver disease in conjunction with candidate hepatocellular carcinoma biomarker GP73.
Interleukin-6 and oncostatin M are elevated in liver disease in conjunction with candidate hepatocellular carcinoma biomarker GP73.
复制标题
DOI：
10.3233/cbm-2012-00276
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Norton PA
中科院分区：
文献类型：
--
作者：
Liang H;Block TM;Wang M;Nefsky B;Long R;Hafner J;Mehta AS;Marrero J;Gish R;Norton PA
高尔基蛋白GP73在肝细胞癌患者的血液循环中升高。它作为HCC生物标志物的有效性受到质疑，因为也有报道称它在肝硬化患者的血液循环中升高。因此，炎症细胞因子对GP73的调控是我们感兴趣的。研究了白细胞介素-6 （IL-6）家族细胞因子对人肝母细胞瘤HepG2细胞中GP73 mRNA和/或蛋白水平的影响。在HepG2细胞中，用促炎细胞因子IL-6或相关细胞因子抑癌素M （OSM）处理后，GP73 mRNA和蛋白水平上调。诱导需要共享受体亚基gp130，并且与STAT3酪氨酸磷酸化增加相关。在蛋白质合成抑制剂环己亚胺存在的情况下，没有观察到最大的细胞因子介导的诱导，这表明其他调节因子起重要作用。ELISA检测恶性前期肝病患者血清中GP73和IL-6水平显示这两种蛋白的循环水平之间存在显著相关性。同样，开发了一种灵敏的ELISA法来测量循环OSM。肝硬化或HCC患者血清中OSM水平相对于无肝病的对照组升高6-7倍。虽然肝硬化患者血清中GP73水平与OSM水平存在关联，但在HCC中没有统计学意义上的相关性，这表明细胞因子在决定循环水平中的作用可能是复杂的。据我们所知，这是第一个与肝脏疾病相关的OSM升高的报告。
The Golgi phosphoprotein GP73 is elevated in the circulation of individuals with a diagnosis of hepatocellular carcinoma. Its usefulness as a biomarker of HCC is questioned, since it has also been reported to be elevated in the circulation of people with liver cirrhosis. Regulation of GP73 by inflammatory cytokines is therefore of interest. The interleukin-6 (IL-6) family cytokines were tested for effects on GP73 mRNA and/or protein levels in human hepatoblastoma HepG2 cells. Levels of GP73 mRNA and protein were up-regulated in HepG2 cells following treatment with either proinflammatory cytokine IL-6 or the related cytokine oncostatin M (OSM). Induction required the shared receptor subunit gp130, and correlated with increased tyrosine phosphorylation of STAT3. Maximal cytokine-mediated induction was not observed in the presence of protein synthesis inhibitor cycloheximide, suggesting additional regulatory factors play an important role. ELISA measurement of GP73 and IL-6 levels in the sera of patients with pre-malignant liver disease revealed a significant correlation between circulating levels of the two proteins. Similarly, a sensitive ELISA assay was developed to measure circulating OSM. OSM levels were elevated 6–7 fold in sera from patients with either cirrhosis or HCC relative to controls without liver disease. Although there was an association between levels of GP73 and OSM in serum from people with liver cirrhosis, there was not a statistically significant correlation in HCC, suggesting that the role of the cytokines in determining circulating levels may be complex. To our knowledge, this is the first report of OSM elevation being associated with liver disease.