Studies on genomic polymorphisms determining host immune reactions against viral infection and interferon therapy

基因组多态性决定宿主针对病毒感染和干扰素治疗的免疫反应的研究

• 批准号: 13670558
• 负责人: SAITO Hidetsugu
• 金额: $ 2.56万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670558/
• 关键词: chronic hepatitis C; hepatitis C virus infection; interferon therapy; IRF-1 gene polymorphisms; promoter activity; T helper function; response to the therapy; インターフェロン治療; C型肝炎ウイルス感染; Tヘルパー細胞機能; 治療反応性; 生化学的治療反応; C型ウイルス感染; Th1; Th2細胞; IRF-1 /

Interferon regulatory factor (IRF)-1 has been indispensable for the functional activation of T helper 1 (Th1) cytokine release. We investigated promoter polymorphisms (single nucleotide polymorphisms ; SNPs) in the IRF-1 gene to see correlation between SNP types and response to the interferon (IFN) therapy or host immune reaction. Host immune reaction significantly differed according to the SNP types possessed by the host. Th1 reaction was strongly activated with administration of IFN in the host possessing one SNP type, but Th2 reaction was predominant in the host possessing the other type of SNP. These results suggested that the prediction of the host immune reaction in the HCV infection might be possible by checking IRF-1 promoter SNP types, especially in the patients with chronic hepatitis C treated with IFN. Because Th1 function is beneficial for viral elimination and Th2 function may regulate inflammation in the liver. However, the people with Th1-dominant type were few and this SNP types could not explain the response to IFN therapy in the patients. Further investigation including promoter SNPs in the other various cytokines is necessary for clarifying the exact prediction of the IFN therapy in patients with chronic hepatitis C.

干扰素调节因子 (IRF)-1 对于 T 辅助细胞 1 (Th1) 细胞因子释放的功能激活是不可或缺的。我们研究了 IRF-1 基因中的启动子多态性（单核苷酸多态性；SNP），以了解 SNP 类型与干扰素 (IFN) 治疗或宿主免疫反应的反应之间的相关性。宿主的免疫反应根据宿主所拥有的SNP类型而显着不同。在具有一种SNP类型的宿主中，通过给予IFN，Th1反应被强烈激活，但在具有另一种类型的SNP的宿主中，Th2反应占主导地位。这些结果表明，通过检查 IRF-1 启动子 SNP 类型，可能可以预测 HCV 感染中的宿主免疫反应，特别是在接受 IFN 治疗的慢性丙型肝炎患者中。因为Th1功能有利于病毒消除，而Th2功能可能调节肝脏炎症。然而，Th1主导型的人很少，这种SNP类型不能解释患者对IFN治疗的反应。包括其他各种细胞因子中的启动子 SNP 在内的进一步研究对于澄清慢性丙型肝炎患者 IFN 治疗的准确预测是必要的。

项目成果

Saito H: "Extrahepatic manifestation in hepatitis C"Jpn.Med.Assoc.J. (JMAJ). 45(12). 526-531 (2002)

Saito H：“丙型肝炎的肝外表现”Jpn.Med.Assoc.J。

Saito H, Tada S, Wakabayashi K, et al.: "The detection of IRF-1 promoter polymorphisms and their possible contribution to T helper response in chronic hepatitis C"J. Interferon Cytokine Res.. 22. 693-700 (2002)

Saito H、Tada S、Wakabayashi K 等人：“IRF-1 启动子多态性的检测及其对慢性丙型肝炎 T 辅助反应的可能贡献”J。

Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S: "Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis"Proc.Natl.Aca

Saito Y、Kanai Y、Sakamoto M、Saito H、Ishii H、Hirohashi S：“DNA 甲基转移酶 3b、DNMT3b4 剪接变体的过度表达，与人类肝癌发生过程中着丝粒周围卫星区域的 DNA 低甲基化相关”Proc.Natl.Aca

H.Saito, H.Ebinuma, H.Nagata, Y.Inagaki, N.Nakamoto, Y.Saito, K.Wakabayashi, T.Takagi, M.Nakamura, H.Katsura, Y.Oguchi, H.Ishii: "Interferon-associated retinopathy in a uniform regimen of natural interferon-α therapy for chronic hepatitis C"Liver. 21. 192

H.Saito、H.Ebinuma、H.Nagata、Y.Inagaki、N.Nakamoto、Y.Saito、K.Wakabayashi、T.Takagi、M.Nakamura、H.Katsura、Y.Oguchi、H.Ishii：“干扰素-天然干扰素-α 治疗慢性丙型肝炎的统一方案中的相关视网膜病变“肝脏”。21. 192

H.Ebinuma, H.Saito, K.Wakabayashi, Y.Saito, T.Takagi, N.Nakamoto, S.Kurita, T.Okuyama, H.Ishii: "Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells"J.Cell.Physiol.. 188. 56-66 (200

H.Ebinuma、H.Saito、K.Wakabayashi、Y.Saito、T.Takagi、N.Nakamoto、S.Kurita、T.Okuyama、H.Ishii：“Cre/下通过反义方法减少 c-myc 表达”