Systemic and local expression levels of TNF-like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis

Authors

  • Yoshihiro Aiba,

    1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
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  • Kenichi Harada,

    1. Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
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  • Atsumasa Komori,

    1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
    2. Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
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  • Masahiro Ito,

    1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
    2. Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
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  • Shinji Shimoda,

    1. Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
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  • Hitomi Nakamura,

    1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
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  • Shinya Nagaoka,

    1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
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  • Seigo Abiru,

    1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
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  • Kiyoshi Migita,

    1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
    2. Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
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  • Hiromi Ishibashi,

    1. International University of Health and Welfare/Fukuoka Sanno Hospital, Fukuoka, Japan
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  • Yasuni Nakanuma,

    1. Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
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  • Nao Nishida,

    1. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Minae Kawashima,

    1. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Katsushi Tokunaga,

    1. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Hiroshi Yatsuhashi,

    1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
    2. Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
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  • Minoru Nakamura

    Corresponding author
    1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
    2. Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan
    3. Headquarters of PBC Research in the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Omura, Japan
    • Correspondence

      Minoru Nakamura, MD, PhD, Headquarters of PBC Research in NHOSLJ, Clinical Research Center, National Hospital Organization Nagasaki Medical Center and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan

      Tel: +81 957 52 3121

      Fax: +81 957 53 6675

      e-mail: nakamuram@nmc.hosp.go.jp

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Abstract

Background & Aims

Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC.

Methods

We analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining.

Results

Serum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients.

Conclusions

These results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC.

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