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Hepcidin is an antibacterial, stress-inducible peptide of the biliary system.

Strnad P, Schwarz P, Rasenack MC, Kucukoglu O, Habib RI, Heuberger D, Ehehalt R, Müller MW, Stiehl A, Adler G, Kulaksiz H - PLoS ONE (2011)

Bottom Line: 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.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.In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively).

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany.

ABSTRACT

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<0.05).

Conclusion: Hepcidin 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.

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Related in: MedlinePlus

Prohepcidin levels are upregulated in cholangitis patients and correlate with the extent of cholestasis.(A) Prohepcidin concentration was measured in bile of PSC patients with acute cholangitis (PSC-cholangitis) or PSC patients with sterile bile (PSC-control) by ELISA. The diagnosis of acute cholangitis was based on the presence of enterobacter in the bile culture together with elevated CRP and/or bilirubin levels. Note that prohepcidin was upregulated in bile of patients with acute cholangitis (p = 0.03). (B) Pearson Product Moment correlation revealed significant positive correlation between prohepcidin and C-reactive protein (CRP) levels (r = 0.48, p = 0.03) as well as between prohepcidin and bilirubin levels (r = 0.71, p = 0.0002) in serum of PSC cholangitis patients (black squares and line), while no correlation was observed in PSC controls (grey triangles and line).
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pone-0016454-g006: Prohepcidin levels are upregulated in cholangitis patients and correlate with the extent of cholestasis.(A) Prohepcidin concentration was measured in bile of PSC patients with acute cholangitis (PSC-cholangitis) or PSC patients with sterile bile (PSC-control) by ELISA. The diagnosis of acute cholangitis was based on the presence of enterobacter in the bile culture together with elevated CRP and/or bilirubin levels. Note that prohepcidin was upregulated in bile of patients with acute cholangitis (p = 0.03). (B) Pearson Product Moment correlation revealed significant positive correlation between prohepcidin and C-reactive protein (CRP) levels (r = 0.48, p = 0.03) as well as between prohepcidin and bilirubin levels (r = 0.71, p = 0.0002) in serum of PSC cholangitis patients (black squares and line), while no correlation was observed in PSC controls (grey triangles and line).

Mentions: To test, whether elevated tissue expression of prohepcidin in the gallbladder epithelia is also translated into increased biliary hepcidin levels, we measured prohepcidin peptide levels in PSC patients with and without a bacterial cholangitis using a previously established prohepcidin ELISA assay [19]. In patients with no apparent biliary infection, prohepcidin levels were below 70 ng/ml (median value 8.9), whereas significantly higher levels were seen in patients with acute cholangitis (up to 240 ng/ml; median value 22.3, p = 0.03; Fig. 6A). Moreover, in PSC patient with cholangitis, prohepcidin levels correlated with CRP (r = 0.48, p = 0.03) and bilirubin serum levels (r = 0.71, p = 0.0002, Fig. 6B,C) thereby suggesting that prohepcidin levels in the bile reflect the extent of biliary infection. Of note, no correlation between prohepcidin, CRP and bilirubin levels was observed in PSC controls, i.e. patients with chronic liver disorder without presence of bacterial infection.


Hepcidin is an antibacterial, stress-inducible peptide of the biliary system.

Strnad P, Schwarz P, Rasenack MC, Kucukoglu O, Habib RI, Heuberger D, Ehehalt R, Müller MW, Stiehl A, Adler G, Kulaksiz H - PLoS ONE (2011)

Prohepcidin levels are upregulated in cholangitis patients and correlate with the extent of cholestasis.(A) Prohepcidin concentration was measured in bile of PSC patients with acute cholangitis (PSC-cholangitis) or PSC patients with sterile bile (PSC-control) by ELISA. The diagnosis of acute cholangitis was based on the presence of enterobacter in the bile culture together with elevated CRP and/or bilirubin levels. Note that prohepcidin was upregulated in bile of patients with acute cholangitis (p = 0.03). (B) Pearson Product Moment correlation revealed significant positive correlation between prohepcidin and C-reactive protein (CRP) levels (r = 0.48, p = 0.03) as well as between prohepcidin and bilirubin levels (r = 0.71, p = 0.0002) in serum of PSC cholangitis patients (black squares and line), while no correlation was observed in PSC controls (grey triangles and line).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3025980&req=5

pone-0016454-g006: Prohepcidin levels are upregulated in cholangitis patients and correlate with the extent of cholestasis.(A) Prohepcidin concentration was measured in bile of PSC patients with acute cholangitis (PSC-cholangitis) or PSC patients with sterile bile (PSC-control) by ELISA. The diagnosis of acute cholangitis was based on the presence of enterobacter in the bile culture together with elevated CRP and/or bilirubin levels. Note that prohepcidin was upregulated in bile of patients with acute cholangitis (p = 0.03). (B) Pearson Product Moment correlation revealed significant positive correlation between prohepcidin and C-reactive protein (CRP) levels (r = 0.48, p = 0.03) as well as between prohepcidin and bilirubin levels (r = 0.71, p = 0.0002) in serum of PSC cholangitis patients (black squares and line), while no correlation was observed in PSC controls (grey triangles and line).
Mentions: To test, whether elevated tissue expression of prohepcidin in the gallbladder epithelia is also translated into increased biliary hepcidin levels, we measured prohepcidin peptide levels in PSC patients with and without a bacterial cholangitis using a previously established prohepcidin ELISA assay [19]. In patients with no apparent biliary infection, prohepcidin levels were below 70 ng/ml (median value 8.9), whereas significantly higher levels were seen in patients with acute cholangitis (up to 240 ng/ml; median value 22.3, p = 0.03; Fig. 6A). Moreover, in PSC patient with cholangitis, prohepcidin levels correlated with CRP (r = 0.48, p = 0.03) and bilirubin serum levels (r = 0.71, p = 0.0002, Fig. 6B,C) thereby suggesting that prohepcidin levels in the bile reflect the extent of biliary infection. Of note, no correlation between prohepcidin, CRP and bilirubin levels was observed in PSC controls, i.e. patients with chronic liver disorder without presence of bacterial infection.

Bottom Line: 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.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.In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively).

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany.

ABSTRACT

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<0.05).

Conclusion: Hepcidin 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.

Show MeSH
Related in: MedlinePlus