Susceptibility of experimental autoimmune hepatitis in transgenic mice overexpressing the c-H-ras gene

Satoshi Tsunematsu, Hidetsugu Saito, Shinichiro Tada, Hirotoshi Ebinuma, Masaharu Tsuchiya, Naoki Kumagai, Toshio Morizane, Tatsuji Nomura, Hiromasa Ishii

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Results from a recent study of ours have demonstrated the significant role of the wild-type ras gene in the development of hepatocellular carcinoma in rasH2 mice having prototype human c-H-ras genes. Chronic cell death and regeneration have been considered to work as co-carcinogens with wild-type ras gene overexpression in this model. To elucidate a role of gene overexpression in the occurrence of chronic inflammation, we tried to induce inflammation in the liver of rasH2 mice by immunizing them with the supernatant of a freshly prepared syngenic liver homogenate. Immunization resulted in a dense inflammatory infiltrate in the portal tract and focal necrosis with spots of fatty or foamy degeneration in the transgenic mouse liver; however, these observations were less frequently observed in non- transgenic mouse liver. Monocytes, granulocytes and plasma cell infiltration were observed in the livers of transgenic mice. An immunohistochemical study showed that CD3-positive lymphocytes also infiltrated the liver. The inflammatory infiltrate was still present in the transgenic liver 24 weeks after the last injection, but little infiltrate was observed at the same time in non-transgenic mice. No hepatic tumours could be produced over the 6 months duration of the study and the results are only preliminary. However, these results do suggest that overexpression of wild-type ras is partially responsible for the occurrence of autoimmune chronic hepatitis.

Original languageEnglish
Pages (from-to)319-324
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume12
Issue number4
Publication statusPublished - 1997

Fingerprint

Autoimmune Hepatitis
ras Genes
Transgenic Mice
Liver
Inflammation
Plasma Cells
Granulocytes
Carcinogens
Regeneration
Monocytes
Hepatocellular Carcinoma
Immunization
Cell Death
Necrosis
Lymphocytes
Injections

Keywords

  • experimental autoimmune hepatitis
  • H-ras
  • transgenic mouse

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Susceptibility of experimental autoimmune hepatitis in transgenic mice overexpressing the c-H-ras gene. / Tsunematsu, Satoshi; Saito, Hidetsugu; Tada, Shinichiro; Ebinuma, Hirotoshi; Tsuchiya, Masaharu; Kumagai, Naoki; Morizane, Toshio; Nomura, Tatsuji; Ishii, Hiromasa.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 12, No. 4, 1997, p. 319-324.

Research output: Contribution to journalArticle

Tsunematsu, S, Saito, H, Tada, S, Ebinuma, H, Tsuchiya, M, Kumagai, N, Morizane, T, Nomura, T & Ishii, H 1997, 'Susceptibility of experimental autoimmune hepatitis in transgenic mice overexpressing the c-H-ras gene', Journal of Gastroenterology and Hepatology (Australia), vol. 12, no. 4, pp. 319-324.
Tsunematsu, Satoshi ; Saito, Hidetsugu ; Tada, Shinichiro ; Ebinuma, Hirotoshi ; Tsuchiya, Masaharu ; Kumagai, Naoki ; Morizane, Toshio ; Nomura, Tatsuji ; Ishii, Hiromasa. / Susceptibility of experimental autoimmune hepatitis in transgenic mice overexpressing the c-H-ras gene. In: Journal of Gastroenterology and Hepatology (Australia). 1997 ; Vol. 12, No. 4. pp. 319-324.
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