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

Abstract

Background/AimsHepcidin (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.MethodsExpression 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.ResultsHepcidin 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<0.05).ConclusionHepcidin is a stress-inducible peptide of the biliary epithelia and a potential marker of biliary stress. In the bile, hepcidin may serve local functions such as protection from bacterial infections.

Hepcidin is localised in gastric parietal cells, regulates acid secretion and is induced byHelicobacter pyloriinfection

“…Our data indicate that hepcidin expression in the stomach is IL-6-inducible, which is well in line with previous findings demonstrating that IL-6/STAT3 pathway is responsible for hepcidin upregulation in multiple tissues such as the liver, heart, biliary system as well as β-cells of pancreas and monocytes 3 9 12 34–36. IL-6/STAT3 pathway is also likely involved in the observed induction of gastric hepcidin in H pylori -infected cells/patients given that these conditions are associated with increased IL-6 levels 37–39.…”

“…Moreover, hepcidin was detected in human gastric juice (data not shown), which opens up the possibility that it might be released into the gastric lumen rather than the bloodstream. Although an exocrine secretion of hepcidin remains to be convincingly demonstrated, the presence of hepcidin in multiple body fluids such as saliva, pleura and ascites fluid as well as bile is consistent with this hypothesis 12 42. Another support for a luminal function of hepcidin in the gut came from a recent paper, which identified DMT1, a protein found at the apical membrane of enterocytes, as a novel hepcidin target 43.…”

Identification of new altered genes in rat cochleae with noise-induced hearing loss

“…Although previous reports have indicated a relationship between iron homeostasis and the auditory systems, the exact function in this process remains to be clarified (Cetin et al, 2004;Strnad et al, 2011).…”

IL-22 Induces an Acute-Phase Response Associated to a Cohort of Acute Phase Proteins and Antimicrobial Peptides as Players of Homeostasis

“…Hepcidin is a stress-inducible peptide of the biliary epithelia. In the bile, hepcidin help to protect against bacterial infections (Strnad et al, 2011). Studies in transgenic mice confirmed that C-reactive protein is protective against microbial pathogens thru its in vitro ability to bind microbes, activating the complement classical and alternative pathways as well as Fc RII (Szalai, 2002).…”