Susceptibility of experimental autoimmune hepatitis in transgenic mice overexpressing the c-H-ras gene.
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.
Tsunematsu
S
S
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Saito
H
H
Tada
S
S
Ebinuma
H
H
Tsuchiya
M
M
Kumagai
N
N
Morizane
T
T
Nomura
T
T
Ishii
H
H
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D011905:Genes, ras; D006520:Hepatitis, Animal / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007114:Immunization; D008099:Liver / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic
D001219:Aspartate Aminotransferases