Human betadefensins (hBDs) are important antimicrobial peptides that contribute to innate immu-nityatmucosals~.Thisstu~wasundertacentoinv~theexpressionofhBD-l andhBD-2 in intrahepatic biliary epithelial cells in specimens of human liver, and 4 cultured cell lines (2 consisting of biliary epithelial & and 2 cholangiocarchoma &). In addition, hBD-1 and hBD-2 were assayed in specimens of bilc hBD-1 was nonspecificay. expressed immunohistochemidy in intrahepatic biliary epithelium and hepatocytes in all patients studied, but expression of hBD-2 was restricted to huge intrahepatic bile ducts in 8 of 10 patients with d e p a t i c biliary obstruction (EBO), 7 of 11 with hepatolithiasis, 1 of 6 with primary biliary cirrhosis (PBC), 1 of 5 with primary sclerosing cholangitis (PSC), 0 of 6 with chronic hepatitis C (CH-C), and 0 of 11 with n o d hepatic reactive protein levels correlated with biliary epithelial expression of hBD-2. Real-time PCR revealed that in all of 28 specimens of fresh liver, including specimens from patients with hepatolithiask, PBC, PSC, CH-C and normal hepatic histology, hBD-1 messenger RNA was consistently expressed, whereas hBD-2 messenger RNA was selectively expressed in biliacy epithehn of patients with hepatolithiasis. Immunobloting analysis revealed hBD-2 protein in bile in 1 of 3 patients with PSC, 1 of 3 with PBC, and each of 6 with hepatolithiasis; in contrast, hBD-1 was detectable in all bile samples examined. Fourculturedbili..yepithelial cell lines consistently expressedhBD-1; in contrast these cell lines did not express hBD-2 spontaneously but w e r e induced to express hBD-2 by treatment with Ecchericia COG lipopoh/saccharide, interleukin-lfl or tumor necTosis factor-a, In conclusion, these findings suggest that in the intrahepatic biliary tree, hBD-2 is expressed in response to local infection and/or active inflammation, whereas hBD-1 may constitute a preexhhg component of the biliary antimicrobial defense system. S u p p h a y -fi this article can be+& on the ~?EPATOL OGY webs& F ~: / / / ; . t . . s . i . . . w ~ . ~~a ~/ O 2 7 ~9 1 3 9 / ~~b ~) . (HEPATOLOGY 2004; 40:925-932.)
histology. hBD-2 expression was evident in bile ducts exhibiting active inflammahl 'on. serum c uman bile is sterile under normal conditions. However, there have been several reports that H bacterial components, such as lipopolysaccharide (LPS), may be detected in normal bile. '-3 Further-