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      Systemic levels of human β-defensin 1 are elevated in patients with cirrhosis

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          Abstract

          Background

          Bacterial translocation (BT) commonly occurs in cirrhosis. Reliable biomarkers for BT are currently lacking. Human beta defensin-1 (hBD-1) is a member of the family of natural antimicrobial peptides produced by epithelial cells and participates in the mucosal defensive mechanisms that prevent BT. The aim of the present study was to examine the local and systemic expression of hBD-1 in patients with cirrhosis.

          Methods

          Plasma concentrations of hBD-1 and of soluble CD14 (sCD14) proteins were measured by ELISA in patients with chronic viral hepatitis, cirrhosis, and healthy controls. Relative mRNA expression of various natural antimicrobial peptides was determined by real-time PCR in biopsies from the terminal ileum and colon.

          Results

          We found significant upregulation of hBD-1 and sCD14 in the peripheral blood of patients with cirrhosis compared to patients with chronic viral hepatitis and healthy controls. The etiology of cirrhosis did not affect the concentration of either protein. The levels of hBD-1 protein correlated significantly with the levels of sCD14 in blood collected from hepatic veins of cirrhotic patients. In contrast, no significant differences were observed in the intestinal mucosal mRNA expression of the Paneth cell specific defensin A5 or hBD-1 between patients with cirrhosis and healthy controls.

          Conclusions

          hBD-1 is upregulated in patients with cirrhosis and highly correlates with the lipopolysaccharide-induced protein sCD14. hBD-1 may serve as a biomarker of BT in patients with cirrhosis.

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          Most cited references31

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          Defensins: antimicrobial peptides of innate immunity.

          Tomas Ganz (2003)
          The production of natural antibiotic peptides has emerged as an important mechanism of innate immunity in plants and animals. Defensins are diverse members of a large family of antimicrobial peptides, contributing to the antimicrobial action of granulocytes, mucosal host defence in the small intestine and epithelial host defence in the skin and elsewhere. This review, inspired by a spate of recent studies of defensins in human diseases and animal models, focuses on the biological function of defensins.
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            The role of cationic antimicrobial peptides in innate host defences.

            Cationic antimicrobial peptides are found in all living species. A single animal can contain >24 different antimicrobial peptides, which fall into four structural classes. These peptides are produced in large quantities at sites of infection and/or inflammation and can have broad-spectrum antibacterial, antifungal, antiviral, antiprotozoan and antisepsis properties. In addition, they interact directly with host cells to modulate the inflammatory process and innate defences.
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              Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria.

              Paneth cells in mouse small intestinal crypts secrete granules rich in microbicidal peptides when exposed to bacteria or bacterial antigens. The dose-dependent secretion occurs within minutes and alpha-defensins, or cryptdins, account for 70% of the released bactericidal peptide activity. Gram-negative bacteria, Gram-positive bacteria, lipopolysaccharide, lipoteichoic acid, lipid A and muramyl dipeptide elicit cryptdin secretion. Live fungi and protozoa, however, do not stimulate degranulation. Thus intestinal Paneth cells contribute to innate immunity by sensing bacteria and bacterial antigens, and discharge microbicidal peptides at effective concentrations accordingly.
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                Author and article information

                Journal
                Ann Gastroenterol
                Ann Gastroenterol
                AnnGastroenterol
                Annals of Gastroenterology : Quarterly Publication of the Hellenic Society of Gastroenterology
                Hellenic Society of Gastroenterology (Greece )
                1108-7471
                1792-7463
                Jan-Mar 2016
                : 29
                : 1
                : 63-70
                Affiliations
                [a ]Department of Gastroenterology (Garyfallia Kaltsa, Giorgos Bamias, Spyros I. Siakavellas, Dimitris Karagiannakis, Jiannis Vlachogiannakos, Irene Vafiadi, Spiros D. Ladas)
                [b ]First Department of Internal Medicine, Propedeutic, Infectious Diseases Research Laboratory (Dimitris Goukos, George L. Daikos), Kapodistrian University of Athens, Laikon Hospital
                [c ]Department of Gastroenterology, Alexandra General Hospital (Evanthia Zampeli, Spyridon Michopoulos), Athens, Greece
                Author notes
                Correspondence to: Garyfallia Kaltsa, MD, Academic Department of Gastroenterology, Ethnikon and Kapodistriakon University, School of Medical Sciences, Laikon General Hospital, 17 Agiou Thoma Street, Athens 11527, Greece, Fax: +30 210 7791839, e-mail: garykaltsa@ 123456gmail.com
                Article
                AnnGastroenterol-29-63
                4700849
                26751578
                3bff796d-013a-4ae4-84a4-f6b9202d95ef
                Copyright: © Hellenic Society of Gastroenterology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 April 2015
                : 01 July 2015
                Categories
                Original Article

                cirrhosis,bacterial translocation,human beta defensin-1,soluble cd14,natural antimicrobial peptides,biomarkers

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