Intrahepatic biliary epithelial cell damage and inflammation in portal tract in association with chronic colitis-harboring TCRalpha(-/-) mice.
BACKGROUND
Intrahepatic bile ducts are the target for inflammation in both primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The mechanisms of biliary epithelial cell damage in both diseases are not clearly understood. Ulcerative colitis (UC) is one of the known complications in PSC. In this study, we assessed the possible influence of apoptosis inhibitor expressed by macrophages (AIM) on intrahepatic bile ducts in the chronic colitis-harboring condition by generating T cell receptor alpha-deficient (TCRalpha(-/-))xAIM-deficient (AIM(-/-)) double-knockout mice.


METHODS
TCRalpha(-/-)xAIM(-/-) mice were generated by crossbreeding TCRalpha(-/-) mice with AIM(-/-) mice. At 24 weeks of age, mice were sacrificed to obtain liver tissues for pathological examinations, and blood was collected to study the serum levels of IgG, IgM and IgA.


RESULTS
In female TCRalpha(-/-)xAIM(-/-) mouse livers, mixed cellular infiltration in the portal area and epithelial cell damage in bile ducts were observed, when compared with female TCRalpha(-/-)xAIM(+/-) and male TCRalpha(-/-)xAIM(-/-) mice. Inflammation in hepatic parenchyma was mild to none in all mice. In the female mouse group, the serum IgA level was relatively increased in TCRalpha(-/-)xAIM(-/-) mice compared to TCRalpha(-/-)xAIM(+/-) mice.


CONCLUSIONS
The defect of AIM might be involved not only in colonic mucosal inflammation but also in portal inflammation, as well as in biliary epithelial cell damage in the livers of female TCRalpha(-/-)xAIM(-/-) mice.
Haruta
Ikuko
I
Department of Medicine and Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Hashimoto
Etsuko
E
Kato
Yoichiro
Y
Miyakawa
Hiroshi
H
Shibata
Noriyuki
N
Kobayashi
Makio
M
Shiratori
Keiko
K