RRC ID 6630
Author Haruta I, Kikuchi K, Hashimoto E, Nakamura M, Miyakawa H, Hirota K, Shibata N, Kato H, Arimura Y, Kato Y, Uchiyama T, Nagamune H, Kobayashi M, Miyake Y, Shiratori K, Yagi J.
Title Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation.
Journal Lab. Invest.
Abstract Bacterial infection has become a focus of attention in the pathogenesis of primary biliary cirrhosis (PBC). We earlier reported that the bacterial lipoteichoic acid was detected at the sites of inflammation around damaged bile ducts in the livers of PBC, and PBC patients' sera showed high titers against streptococcal histone-like protein. Here, we investigated whether chronic bacterial exposure could trigger PBC-like epithelial cell damage in normal mouse. BALB/c mice were repeatedly inoculated with various bacteria for 8 weeks. At 1 week (Group 1) and 3, 4, or 20 months (long term; Group 2) after the final inoculation, mice were killed to obtain samples. In the livers of the Streptococcus intermedius (S.i.)-inoculated mice in Group 1, cellular infiltration was predominantly observed around the bile ducts over the hepatic parenchyma. In the S.i.-inoculated mice in Group 2, portal but not parenchymal inflammation was observed in the livers, and periductal cellular infiltrates were detected in the salivary glands. Both S.i.-inoculated Groups 1 and 2 BALB/c mice sera had antibodies against HuCCT1 biliary epithelial cells, anti-nuclear antibodies, and anti-gp210 antibodies, but not anti-mitochondrial antibodies. Immunoreactivity to histone-like DNA-binding protein of S.i. (S.i.-HLP) was detectable around the sites of chronic nonsuppurative destructive cholangitis in the portal area in the livers of both S.i.-inoculated Groups 1 and 2 BALB/c mice. Furthermore, anti-S.i.-HLP antibody bound to synthetic gp210 peptide, as well. Bacteria triggered PBC-like cholangitis, multifocal epithelial inflammation, and autoantibody production. Bacteria are likely involved in the pathogenesis of PBC and of associated multifocal epithelial inflammation.
Volume 90(4)
Pages 577-88
Published 2010-4
DOI 10.1038/labinvest.2010.40
PII labinvest201040
PMID 20142809
MeSH Animals Antibodies, Antinuclear / physiology* Disease Models, Animal Epithelial Cells / immunology Immunity, Innate / immunology Inflammation / microbiology Inflammation / physiopathology Liver Cirrhosis, Biliary / immunology* Liver Cirrhosis, Biliary / microbiology* Liver Cirrhosis, Biliary / physiopathology Mice Mice, Inbred BALB C Nuclear Pore Complex Proteins / immunology Streptococcus intermedius / immunology* Streptococcus intermedius / pathogenicity
IF 3.684
Times Cited 14
Human and Animal Cells