Peptide antibiotic human beta‐defensin‐1 and ‐2 contribute to antimicrobial defense of the intrahepatic biliary tree | Zendy

Harada Kenichi | Zendy; Ohba Kazuo | Zendy; Ozaki Satoru | Zendy; Isse Kumiko | Zendy; Hirayama Toshiya | Zendy; Wada Akihiro | Zendy; Nakanuma Yasuni | Zendy

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Peptide antibiotic human beta‐defensin‐1 and ‐2 contribute to antimicrobial defense of the intrahepatic biliary tree

Author(s) -

Harada Kenichi,

Ohba Kazuo,

Ozaki Satoru,

Isse Kumiko,

Hirayama Toshiya,

Wada Akihiro,

Nakanuma Yasuni

Publication year - 2004

Publication title -

hepatology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.488

H-Index - 361

eISSN - 1527-3350

pISSN - 0270-9139

DOI - 10.1002/hep.20379

Subject(s) - hepatolithiasis , primary sclerosing cholangitis , intrahepatic bile ducts , beta defensin , primary biliary cirrhosis , biliary tract , pathology , immunohistochemistry , defensin , histology , antimicrobial peptides , biology , epithelium , medicine , gastroenterology , bile duct , antimicrobial , microbiology and biotechnology , hepatectomy , surgery , disease , resection

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.

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