慢性乙型肝炎和肝细胞癌土拨鼠白细胞介素8的特征分析

Characterization of interleukin 8 in woodchucks with chronic hepatitis B and hepatocellular carcinoma.

作者信息

Liu C-J, Huang Y-J, Chen H-L, Lin H-T, Lin H-L, Kuo M-L, Huang J-L, Chen D-S, Chen P-J, Wu H-L

机构信息

Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

Genes Immun. 2009 Jan;10(1):27-36. doi: 10.1038/gene.2008.86. Epub 2008 Oct 30.

DOI:10.1038/gene.2008.86

PMID:18971938

Abstract

The eastern woodchuck, Marmota monax, represents a useful animal model to study hepatitis B virus infection in humans. However, immunological studies in this model have been impeded by a lack of basic information about the components of the immune system such as cytokines and chemokines. To clarify the role(s) of interleukin 8 (IL-8) in chronic hepatitis B and hepatocellular carcinoma (HCC) in the woodchuck model, we cloned and characterized the woodchuck IL-8 cDNA and genomic DNA. Sequence analysis revealed that the organization of the wk-IL-8 gene is similar to that of the human IL-8 gene and consists of four exons and three introns. Woodchuck IL-8 protein exhibits the conserved ELRCXC motif of IL-8 and shows 87, 82, 82 and 79% similarity with rabbit, ovine, bovine and human IL-8 proteins, respectively. The biological activity of wk-IL-8 was demonstrated using neutrophil chemotaxis assays. Wk-IL-8 could be readily detected in both tumor and non-tumor tissues with higher expression in the non-tumor tissues in most cases. The results from this study will facilitate the investigation of IL-8 in the immunopathogenesis of hepadnavirus-related diseases by the woodchuck model.

摘要

东部土拨鼠（Marmota monax）是研究人类乙型肝炎病毒感染的一种有用动物模型。然而，由于缺乏关于免疫系统组成成分（如细胞因子和趋化因子）的基本信息，该模型的免疫学研究受到了阻碍。为了阐明白细胞介素8（IL-8）在土拨鼠模型中慢性乙型肝炎和肝细胞癌（HCC）中的作用，我们克隆并鉴定了土拨鼠IL-8 cDNA和基因组DNA。序列分析表明，土拨鼠IL-8基因（wk-IL-8）的结构与人类IL-8基因相似，由四个外显子和三个内含子组成。土拨鼠IL-8蛋白具有IL-8保守的ELRCXC基序，与兔、羊、牛和人类IL-8蛋白的相似性分别为87%、82%、82%和79%。通过中性粒细胞趋化试验证明了wk-IL-8的生物学活性。在肿瘤组织和非肿瘤组织中均能轻易检测到wk-IL-8，大多数情况下非肿瘤组织中的表达更高。本研究结果将有助于利用土拨鼠模型研究IL-8在嗜肝DNA病毒相关疾病免疫发病机制中的作用。