γ-interferon treatment inhibits collagen deposition in murine schistosomiasis

Authors

  • Mark J. Czaja,

    1. Departments of Medicine, Biochemistry and Pathology and the Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    2. TNO Primate Center, Rijswijk, The Netherlands
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  • Francis R. Weiner,

    1. Departments of Medicine, Biochemistry and Pathology and the Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    2. TNO Primate Center, Rijswijk, The Netherlands
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  • Shizuko Takahashi,

    1. Departments of Medicine, Biochemistry and Pathology and the Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    2. TNO Primate Center, Rijswijk, The Netherlands
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  • Marie-Adele Giambrone,

    1. Departments of Medicine, Biochemistry and Pathology and the Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    2. TNO Primate Center, Rijswijk, The Netherlands
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  • Peter H. Der Van Meide,

    1. Departments of Medicine, Biochemistry and Pathology and the Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    2. TNO Primate Center, Rijswijk, The Netherlands
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  • Huub Schellekens,

    1. Departments of Medicine, Biochemistry and Pathology and the Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    2. TNO Primate Center, Rijswijk, The Netherlands
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  • Luis Biempica,

    1. Departments of Medicine, Biochemistry and Pathology and the Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    2. TNO Primate Center, Rijswijk, The Netherlands
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  • Mark A. Zern M.D.

    Corresponding author
    1. Departments of Medicine, Biochemistry and Pathology and the Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    2. TNO Primate Center, Rijswijk, The Netherlands
    • Department of Medicine, Roger Williams General Hospital, 825 Chalkstone Avenue, Providence, Rhode Island 02908
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Abstract

Since interferons have been shown to affect the synthesis of matrix proteins such as collagen in several in vitro systems, the potential role of γ-interferon in inhibiting hepatic fibrosis was investigated. Hepatic cells, consisting primarily of hepatocytes, were treated with recombinant γ-interferon for 24 hr. Northern blot hybridization showed that γ-interferon treatment caused a profound decrease in pro-α2(I)collagen mRNA levels but an increase in β-actin mRNA content. The effects of γ-interferon were then studied in an in vivo model of hepatic fibrogenesis, murine schistosomiasis. Schistosoma-infected mice were treated with daily i.m. injections of γ-interferon for a 4-week period starting 4 weeks after the initial infection. γ-Interferon treatment decreased collagen deposition as determined by histologic evaluation and measurement of total liver collagen content. Northern blots showed Types I and III procollagen mRNA levels for treated, infected animals to be only 32 and 29% that of infected controls, but β-actin mRNA levels were significantly elevated. These results indicate a potential role for γ-interferon as an antifibrogenic agent in vivo.

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