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Protective effect of hepatocyte growth factor on interferon‐gamma—induced cytotoxicity in mouse hepatocytes
Author(s) -
Morita Masahiko,
Watanabe Yoshifumi,
Akaike Toshihiro
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840210617
Subject(s) - hepatocyte growth factor , dna fragmentation , flow cytometry , hepatocyte , microbiology and biotechnology , cytokine , tumor necrosis factor alpha , apoptosis , biology , cytotoxic t cell , interferon , cytotoxicity , interferon gamma , cancer research , immunology , programmed cell death , biochemistry , in vitro , receptor
We examined the interactive effect of several cytokines (interleukin‐1 beta [IL‐1β], tumor necrosis factor alpha [TNF‐α], interferon gamma [IFN‐γ], IL‐6, IFN‐α/B, and hepatocyte growth factor [HGF]) presumably involved in hepatitis, on primary cultured murine hepatocytes. Among these cytokines, only IFN‐γ induced LDH release from hepatocytes in both time‐ and dose‐dependent fashions. The cytotoxic effect was inhibited by antiserum—containing anti‐mouse IFN‐γ monoclonal antibodies (R4‐6A2). Moreover, intriguingly, IFN‐γ induced DNA fragmentation in the hepatocytes in a time‐ and dose‐dependent fashion according to the gel electrophoresis of genomic DNA and flow cytometry analysis. These results suggest that the cytotoxic effect of IFN‐γ on hepatocytes was caused by inductive apoptosis. The LDH release and DNA fragmentation induced by IFN‐γ were inhibited by HGF in a dose‐dependent manner, whereas they seemed to be accelerated by TNF‐α. Flow cytometry analysis of the nuclei of treated hepatocytes confirmed the interactions in DNA degradation. The DNA synthesis of cultured hepatocytes was also reduced by IFN‐γ but recovered by hepatocyte growth factor. Taken together, IFN‐γ is presumed to be a critical cytokine in hepatic damage, and the network composed of IFN‐γ, TNF‐α, and HGF may play an important role in the regulation of liver injury.