Uprequlation of anti-HCV activity

抗 HCV 活性上调

• 批准号: 12670505
• 负责人: TANAKA Katsuaki
• 金额: $ 1.02万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670505/
• 关键词: Hepatics C virus; Interferon receptor; IFNARI; IFNAR2

Intrahepatic mRNA levels of type-I interferon receptor genes have been shown to correlate with the clinical efficacy of interferon therapy in patients with chronic hepatitis C. Therefore, we first attempted to raise efficiency of interferon for excluding the hepatitis C virus by expressing the interferon receptor genes into the human hepatocyte cell lines. Then, the factor with the possibility of up-regulating the interferon receptor was retrieved. We found that lactoferrin supplementation significantly improved the biochemical and virological responses at the end of interferon treatment in patients with chronic hepatitis C; however, it did not change the PBMC's and the hepatic mRNA levels of type-I interferon receptor genes. Far-Western blot analysis using the lactoferrin fragments and the hepatitis C virus E2 protein revealed the 33 amino acid residues as the minimum binding site in the carboxy1 region of lactoferrin. We furthermore investigated the mechanism of anti-inflammation action of lactoferrin using rat model of acute hepatic failure, and found that plasma and hepatic TNF-α mRNA levels were decreased in rats pretreated by lactoferrin. Lactoferrin is a promising candidate for adjuvant therapy with interferon in patients with chronic hepatitis C through its anti-virus and the anti-inflammatory action.

肝内I型干扰素受体基因的mRNA水平已被证明与慢性丙型肝炎患者干扰素治疗的临床疗效相关。因此，我们首先尝试通过在人肝细胞系中表达干扰素受体基因来提高干扰素排除丙型肝炎病毒的效率。然后，检索可能上调干扰素受体的因子。我们发现，补充乳铁蛋白显著改善了慢性丙型肝炎患者在干扰素治疗结束时的生化和病毒学反应;然而，它并没有改变PBMC和肝脏I型干扰素受体基因的mRNA水平。使用乳铁蛋白片段和丙型肝炎病毒E2蛋白的Far-Western印迹分析揭示了乳铁蛋白的羧基1区域中的33个氨基酸残基作为最小结合位点。我们进一步采用大鼠急性肝衰竭模型研究了乳铁蛋白的抗炎作用机制，发现经乳铁蛋白预处理的大鼠血浆和肝脏TNF-α mRNA水平降低。乳铁蛋白通过其抗病毒和抗炎作用而成为干扰素辅助治疗慢性丙型肝炎患者的一种有前途的候选药物。

项目成果

Ikeda A,Tanaka K, et al.: "Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells."Virus Res. 66. 51-63 (2000)

Ikeda A、Tanaka K 等人：“乳铁蛋白对人类培养细胞中丙型肝炎病毒感染的抗病毒活性的表征。”Virus Res。

Togawa J, Tanaka K, et al.: "Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance"Am J Physiol Gastrointest Liver Physiol. 283. G187-G195 (2002)

Tokawa J、Tanaka K 等人：“乳铁蛋白通过调节免疫系统和纠正细胞因子失衡减少大鼠结肠炎”Am J Physiol Gastrointest Liver Physiol。

Sobao Y, Tanaka K, et al.: "The role of hepatitis B virus-specific memory CD8 T cells in the control of viral replication"J Hepatol. 36. 105-115 (2002)

Sobao Y、Tanaka K 等人：“乙型肝炎病毒特异性记忆 CD8 T 细胞在控制病毒复制中的作用”J Hepatol。

Okada S, Tanaka K, et al.: "Dose-response trial of lactoferrin in patients with chronic hepatitis C"Jpn J Cancer Res. 93. 1063-1069 (2002)

Okada S、Tanaka K 等人：“慢性丙型肝炎患者中乳铁蛋白的剂量反应试验”Jpn J Cancer Res。

Shimamura S, Tanaka K, et al.: "Detection of vascular endothelial growth factor and its receptor expression in human hepatocellular carcinoma biopsy specimens"J Gastroenterol Hepatol. 15. 640-646 (2000)

Shimamura S，Tanaka K，等：“人肝细胞癌活检标本中血管内皮生长因子及其受体表达的检测”J Gastroenterol Hepatol。