Hepcidin Is an Antibacterial, Stress-Inducible Peptide of the Biliary System

Autor: Hasan Kulaksiz, Peggy Schwarz, Michael W. Müller, Robert Ehehalt, Adolf Stiehl, Guido Adler, Maria Rasenack, Ö Kücükoglu, Pavel Strnad, Rayan I. Habib, Dominik Heuberger
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Anatomy and Physiology
Digestive Physiology
lcsh:Medicine
Gastroenterology
chemistry.chemical_compound
Mice
Molecular Cell Biology
lcsh:Science
Biliary Tract
Multidisciplinary
biology
Bile duct
Gallbladder
Anti-Bacterial Agents
medicine.anatomical_structure
Biliary tract
Medicine
HAMP
Cellular Types
Biliary Disorders
Research Article
Transcriptional Activation
medicine.medical_specialty
Cell Physiology
Bilirubin
Cholangitis
Sclerosing

Gastroenterology and Hepatology
digestive system
Microbiology
Primary sclerosing cholangitis
Cholestasis
Hepcidins
Hepcidin
Stress
Physiological

Internal medicine
Microbial Control
medicine
Animals
Humans
Biology
Interleukin-6
lcsh:R
Epithelial Cells
medicine.disease
Endocrinology
chemistry
biology.protein
lcsh:Q
Bile Ducts
Digestive System
Antimicrobial Cationic Peptides
Zdroj: PLoS ONE
PLoS ONE, Vol 6, Iss 1, p e16454 (2011)
ISSN: 1932-6203
Popis: Background/Aims Hepcidin (gene name HAMP), an IL-6-inducible acute phase peptide with antimicrobial properties, is the key negative regulator of iron metabolism. Liver is the primary source of HAMP synthesis, but it is also produced by other tissues such as kidney or heart and is found in body fluids such as urine or cerebrospinal fluid. While the role of hepcidin in biliary system is unknown, a recent study demonstrated that conditional gp130-knockout mice display diminished hepcidin levels and increased rate of biliary infections. Methods Expression and localization of HAMP in biliary system was analyzed by real time RT-PCR, in-situ hybridization, immunostaining and –blotting, while prohepcidin levels in human bile were determined by ELISA. Results Hepcidin was detected in mouse/human gallbladder and bile duct epithelia. Biliary HAMP is stress-inducible, in that it is increased in biliary cell lines upon IL-6 stimulation and in gallbladder mucosa of patients with acute cholecystitis. Hepcidin is also present in the bile and elevated prohepcidin levels were observed in bile of primary sclerosing cholangitis (PSC) patients with concurrent bacterial cholangitis compared to PSC subjects without bacterial infection (median values 22.3 vs. 8.9; p = 0.03). In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively). In vitro, hepcidin enhanced the antimicrobial capacity of human bile (p
Databáze: OpenAIRE