Overexpression of interferon γ-inducible protein 10 in the liver of patients with type I autoimmune hepatitis identified by suppression subtractive hybridization

被引:18
作者
Nagayama, K
Enomoto, N
Miyasaka, Y
Kurosaki, M
Chen, CH
Sakamoto, N
Nakagawa, M
Sato, C
Tazawa, J
Ikeda, T
Izumi, N
Watanabe, M
机构
[1] Tokyo Med & Dent Univ, Fac Med, Dept Gastroenterol & Hepatol, Dept Internal Med 2,Bunkyo Ku, Tokyo 1138519, Japan
[2] Tokyo Med & Dent Univ, Fac Med, Dept Hlth Sci, Tokyo 1138519, Japan
[3] Tsuchiura Kyodo Gen Hosp, Dept Internal Med, Ibaraki, Osaka, Japan
[4] Yokosuka Kyosai Gen Hosp, Dept Internal Med, Kanagawa, Japan
[5] Musashino Red Cross Hosp, Dept Gastroenterol & Hepatol, Tokyo, Japan
关键词
D O I
10.1016/S0002-9270(01)02522-9
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
OBJECTIVE: To clarify gene expression profiles in the liver may elucidate the pathogenesis of type I autoimmune hepatitis (AIH). Using suppression subtractive hybridization (SSH), we identified genes overexpressed in the liver of AIH. METHODS: A small liver biopsy sample from a patient with definite ALH was available to be analyzed in our system. By mixing cDNA synthesized from this sample as a 'tester' and cDNA from a normal liver as a 'driver,' we subtracted cDNA to enrich genes overexpressed in AIH. After polymerase chain reaction (PCR) amplification and subcloning, we identified subtracted genes by sequencing 50 randomly selected clones. RESULTS: Only one cDNA fragment, which is identical to interferon inducible protein 10 (IP-10), was overexpressed by > 10 times in the liver of AIH, as compared with control. We confirmed IP-10 overexpression in all eight patients with AIH by reverse transcription PCR. Immunohistochemical analysis demonstrated increased IP-10 expression in hepatocytes in the liver of AIH. Reverse transcription PCR analysis of 63 liver biopsy samples with various liver diseases revealed that IP-10 expression was significantly higher in AIH (p = 0.025) and chronic hepatitis C (p = 0.0043) than in other liver diseases. Interestingly, the amount of IP-10 mRNA expression was correlated with serum ALT values in AIH (p = 0.0006), but not in chronic hepatitis C (p = 0.43). CONCLUSION: These results indicate the IP-10 expression in the liver might be used as a preferential marker of AIH, and that IP-10 has some pathophysiological roles in the liver damage of AIH. (C) 2001 by Am. Coll. of Gastroenterology.
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页码:2211 / 2217
页数:7
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