RRC ID 10882
著者 Harada K, Ohba K, Ozaki S, Isse K, Hirayama T, Wada A, Nakanuma Y.
タイトル Peptide antibiotic human beta-defensin-1 and -2 contribute to antimicrobial defense of the intrahepatic biliary tree.
ジャーナル Hepatology
Abstract Human beta-defensins (hBDs) are important antimicrobial peptides that contribute to innate immunity at mucosal surfaces. This study was undertaken to investigate the expression of hBD-1 and hBD-2 in intrahepatic biliary epithelial cells in specimens of human liver, and 4 cultured cell lines (2 consisting of biliary epithelial cells and 2 cholangiocarcinoma cells). In addition, hBD-1 and hBD-2 were assayed in specimens of bile. hBD-1 was nonspecifically expressed immunohistochemically in intrahepatic biliary epithelium and hepatocytes in all patients studied, but expression of hBD-2 was restricted to large intrahepatic bile ducts in 8 of 10 patients with extrahepatic 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 normal hepatic histology. hBD-2 expression was evident in bile ducts exhibiting active inflammation. Serum C 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 hepatolithiasis, PBC, PSC, CH-C and normal hepatic histology, hBD-1 messenger RNA was consistently expressed, whereas hBD-2 messenger RNA was selectively expressed in biliary epithelium 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. Four cultured biliary epithelial cell lines consistently expressed hBD-1; in contrast these cell lines did not express hBD-2 spontaneously but were induced to express hBD-2 by treatment with Eschericia coli, lipopolysaccharide, interleukin-1beta or tumor necrosis factor-alpha. 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 preexisting component of the biliary antimicrobial defense system.
巻・号 40(4)
ページ 925-32
公開日 2004-10-1
DOI 10.1002/hep.20379
PMID 15382127
MeSH Adult Aged Bile / metabolism Bile Duct Diseases / metabolism Bile Duct Diseases / physiopathology* Bile Duct Neoplasms Bile Ducts, Intrahepatic / cytology Bile Ducts, Intrahepatic / metabolism* Cell Line, Tumor Cholangiocarcinoma Epithelial Cells / cytology Epithelial Cells / metabolism Female Gene Expression Hepatocytes / cytology Hepatocytes / metabolism Humans In Situ Hybridization Liver Diseases / metabolism Liver Diseases / physiopathology* Male Middle Aged RNA, Messenger / analysis Reverse Transcriptase Polymerase Chain Reaction beta-Defensins / genetics* beta-Defensins / metabolism*
IF 14.679
引用数 72
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞 Hep G2(RCB1648)