Expression of NF-kappaB in rotavirus-induced damage to the liver and biliary tract in neonatal mice.

BACKGROUND

Biliary atresia, the etiology of which still remains unclear, occurs exclusively in newborns and most are infected with rotavirus. In this study, we aimed to investigate the histopathological patterns of different kinds of rotavirus in the liver and biliary tract of neonatal mice and the expression of NF-kappaB in the liver and biliary tract of infected mice.

METHODS

Twenty-three adult mice (8 were male and 15 female) were divided into 8 breeding pairs, and each pair (1 male and 2 females) was housed in a cage in a laminar flow hood. Newborn mice, 24-48 hours old were randomly divided into A, B and C groups. The A and B groups were respectively inoculated with MMU18006 and SA11 rotavirus through the intraperitoneal route, while group C as blank control was only inoculated with culture medium. The liver was dissected after 5, 10, 15, 21 and 28 days; the weight of each mouse and the histopathological patterns in the liver were recorded. The expression of NF-kappaB in the liver and intrahepatic bile ducts was detected by immunohistochemical staining and the expression intensity was analyzed with a GT-2 imaging instrument.

RESULTS

The average increase in weight of infected mice was significantly slower than that of the normal control, while the growth rate of group A (injected with MMU18006 rotavirus) was slower than that of group B (SA11 rotavirus). In infected mice, the acute and chronic inflammation of liver and intra- and extra-hepatic bile ducts was more significant in group A. Stenosis was found in most intrahepatic bile ducts, and sporadically in extrahepatic bile ducts. The expression of NF-kappaB in infected mice was dramatically higher than that of the normal control, while the expression in group A was higher than in group B.

CONCLUSIONS

Significant damage to the liver and biliary tract of neonatal mice can be induced by inoculating MMU18006 rotavirus through the intraperitoneal route, which is very similar to the pathology of biliary atresia in the newborn human. Similar inoculation with SA11 rotavirus can only result in moderate impairment that disappears quickly. The difference of pathogenicity between the two rotaviruses may depend on their differing capacities to increase the expression of NF-kappaB in the liver and biliary tract.