DOI: 10.1046/j.1365-2249.2003.02035.x. Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis

Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis

10.1046/j.1365-2249.2003.02035.x

Crossref journal-article

Oxford University Press (OUP)

Clinical and Experimental Immunology (286)

Abstract

SUMMARYThe impact of chronic inflammation on the expression of human α-defensins 5 and 6 (HD-5, HD-6), β-defensins 1 and 2 (hBD-1, hBD-2) and lysozyme in epithelial cells of small and large intestine was investigated. Intestinal specimens from 16 patients with ulcerative colitis (UC), 14 patients with Crohn's disease (CD) and 40 controls with no history of inflammatory bowel disease were studied. mRNA expression levels of the five defence molecules were determined in freshly isolated epithelial cells by real-time quantitative RT-PCR. Specific copy standards were used allowing comparison between the expression levels of the different defensins. HD-5 and lysozyme protein expression was also studied by immunohistochemistry. Colonic epithelial cells from patients with UC displayed a significant increase of hBD-2, HD-5, HD-6 and lysozyme mRNA as compared to epithelial cells in controls. Lysozyme mRNA was expressed at very high average copy numbers followed by HD-5, HD-6, hBD-1 and hBD-2 mRNA. HD-5 and lysozyme protein was demonstrated in metaplastic Paneth-like cells in UC colon. There was no correlation between hBD-2 mRNA levels and HD-5 or HD-6 mRNA levels in colon epithelial cells of UC patients. Colonic epithelial cells of Crohn's colitis patients showed increased mRNA levels of HD-5 and lysozyme mRNA whereas ileal epithelial cells of Crohn's patients with ileo-caecal inflammation did not. Chronic inflammation in colon results in induction of hBD-2 and α-defensins and increased lysozyme expression. hBD-1 expression levels in colon remain unchanged in colitis. The high antimicrobial activity of epithelial cells in chronic colitis may be a consequence of changes in the epithelial lining, permitting adherence of both pathogenic bacteria and commensals directly to the epithelial cell surface.

Bibliography

FAHLGREN, A., HAMMARSTRÃM, S., DANIELSSON, Ã., & HAMMARSTRÃM, M.-L. (2003). Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis. Clinical and Experimental Immunology, 131(1), 90â101.

Authors 4

A FAHLGREN (first)
S HAMMARSTRÖM (additional)
Å DANIELSSON (additional)
M-L HAMMARSTRÖM (additional)

References 48 Referenced 162

10.1007/PL00000914 / Cell Mol Life Sci / The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity by Yang (2001)
10.1034/j.1600-065X.2000.917301.x / Immunol Rev / Innate immunity and the normal microflora by Boman (2000)
10.1007/s000180050004 / Cell Mol Life Sci / Epithelial antimicrobial peptides: innate local host response elements by Schroder (1999)
10.1016/S0952-7915(99)80005-3 / Curr Opin Immunol / Antimicrobial peptides in mammalian and insect host defence by Lehrer (1999)
10.1016/S0021-9258(18)50079-X / J Biol Chem / Paneth cells of the human small intestine express an antimicrobial peptide gene by Jones (1992)
10.1016/0014-5793(93)81160-2 / FEBS Lett / Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel by Jones (1993)
10.1128/iai.65.6.2389-2395.1997 / Infect Immun / Localization of human intestinal defensin 5 in Paneth cell granules by Porter (1997)
{'key': '2022011222001427000_b8', 'first-page': '1247', 'article-title': 'Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract', 'volume': '152', 'author': 'Quayle', 'year': '1998', 'journal-title': 'Am J Pathol'} / Am J Pathol / Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract by Quayle (1998)
10.1016/S0002-9378(97)70517-9 / Am J Obstet Gynecol / Detection of human defensin 5 in reproductive tissues by Svinarich (1997)
10.1016/0014-5793(95)00687-5 / FEBS Lett / hBD-1: a novel β-defensin from human plasma by Bensch (1995)
10.1038/43088 / Nature / A peptide antibiotic from human skin by Harder (1997)
10.1172/JCI2410 / J Clin Invest / Human β-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung by Bals (1998)
10.1172/JCI1861 / J Clin Invest / Human β-defensin-1: an antimicrobial peptide of urogenital tissues by Valore (1998)
10.4049/jimmunol.163.12.6718 / J Immunol / Expression and regulation of the human β-defensins hBD-1 and hBD-2 in intestinal epithelium by O'Neil (1999)
10.1046/j.1365-2362.2000.00696.x / Eur J Clin Invest / Differential expression of human alpha- and beta-defensins mRNA in gastrointestinal epithelia by Frye (2000)
{'key': '2022011222001427000_b16', 'first-page': '126', 'article-title': 'Lysozyme in Paneth cell secretions', 'volume': '45', 'author': 'Geyer', 'year': '1973', 'journal-title': 'Acta Histochem'} / Acta Histochem / Lysozyme in Paneth cell secretions by Geyer (1973)
10.1007/BF01002560 / Histochem J / The cytochemical localization of lysozyme in Paneth cell granules by Ghoos (1971)
10.1136/jcp.28.2.124 / J Clin Pathol / The distribution of muramidase (lysozyme) in human tissues by Mason (1975)
10.1128/IAI.68.9.5412-5415.2000 / Infect Immun / Regulation of human β-defensins by gastric epithelial cells in response to infection with Helicobacter pylori or stimulation with interleukin-1 by O'Neil (2000)
10.1074/jbc.M000184200 / J Biol Chem / CD14-dependent lipopolysaccharide-induced β-defensin-2 expression in human tracheobronchial epithelium by Becker (2000)
10.1073/pnas.95.25.14961 / Proc Natl Acad Sci USA / Production of β-defensins by human airway epithelia by Singh (1998)
10.1128/IAI.67.6.2740-2745.1999 / Infect Immun / Production of β-defensin antimicrobial peptides by the oral mucosa and salivary glands by Mathews (1999)
10.1016/S0378-1119(98)00480-6 / Gene / Structure and mapping of the human β-defensin HBD-2 gene and its expression at sites of inflammation by Liu (1998)
10.1165/ajrcmb.22.6.4023 / Am J Respir Cell Mol Biol / Mucoid Pseudomonas aeruginosa, TNF-α, and IL-1β, but not IL-6, induce human β-defensin-2 in respiratory epithelia by Harder (2000)
10.1074/jbc.M008557200 / J Biol Chem / Isolation and characterization of human β-defensin-3, a novel human inducible peptide antibiotic by Harder (2001)
10.1096/fj.00-0865fje / FASEB J / Human β-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity by Garcia (2001)
10.1136/gut.48.2.176 / Gut / Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease by Cunliffe (2001)
10.1016/0022-1759(92)90147-L / J Immunol Meth / Isolation of functionally active intraepithelial lymphocytes and enterocytes from human small and large intestine by Lundqvist (1992)
10.4049/jimmunol.157.5.1926 / J Immunol / Intraepithelial lymphocytes in human gut have lytic potential and a cytokine profile that suggest T helper 1 and cytotoxic functions by Lundqvist (1996)
10.1016/0016-5085(94)90015-9 / Gastroenterology / Normal colonic epithelium adheres to carcinoembryonic antigen and type IV collagen by Ishii (1994)
10.1016/0003-2697(87)90021-2 / Anal Biochem / Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction by Chomczynski (1987)
{'key': '2022011222001427000_b32', 'volume-title': 'Molecular biology of the cell', 'author': 'Alberts', 'year': '1994', 'edition': '3rd'} / Molecular biology of the cell by Alberts (1994)
10.1016/S1074-7613(01)00192-3 / Immunity / Biological insights into TCRγδ+ and TCRαβ+ intraepithelial lymphocytes provided by serial analysis of gene expression (SAGE) by Shires (2001)
{'key': '2022011222001427000_b34', 'first-page': '343', 'article-title': 'Paneth cell metaplasia in diseases of the colon and rectum', 'volume': '97', 'author': 'Symonds', 'year': '1974', 'journal-title': 'Arch Pathol'} / Arch Pathol / Paneth cell metaplasia in diseases of the colon and rectum by Symonds (1974)
10.1016/0092-8674(89)90833-7 / Cell / NF-κB: a pleiotropic mediator of inducible and tissue-specific gene control by Lenardo (1989)
10.1172/JCI11830 / J Clin Invest / NF-κB: a key role in inflammatory diseases by Tak (2001)
10.1016/S0006-2952(00)00390-7 / Biochem Pharmacol / Nuclear factor-κ B activation and innate immune response in microbial pathogen infection by Naumann (2000)
10.1152/ajpcell.2000.278.3.C451 / Am J Physiol Cell Physiol / The I-κ B/NF-κ B system: a key determinant of mucosal inflammation and protection by Jobin (2000)
10.4049/jimmunol.164.2.966 / J Immunol / Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors by Cario (2000)
10.1203/00006450-200104000-00023 / Pediatr Res / Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes by Fusunyan (2001)
10.1073/pnas.241308598 / Proc Natl Acad Sci USA / Flagellin stimulation of intestinal epithelial cells triggers CCL20-mediated migration of dendritic cells by Sierro (2001)
10.1128/IAI.68.12.7010-7017.2000 / Infect Immun / Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease by Cario (2000)
10.1016/S0140-6736(96)91563-9 / Lancet / Unifying hypothesis for inflammatory bowel disease and associated colon cancer: sticking the pieces together with sugar by Rhodes (1996)
10.1016/S0016-5085(99)70393-8 / Gastroenterology / The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls by Schultsz (1999)
10.1016/S0966-842X(01)01952-7 / Trends Microbiol / Is there a role for CEA in innate immunity in the colon? by Hammarström (2001)
10.1146/annurev.iy.11.040193.000541 / Ann Rev Immunol / Defensins: antimicrobial and cytotoxic peptides of mammalian cells by Lehrer (1993)
10.1152/ajpcell.2001.280.2.C296 / Am J Physiol Cell Physiol / Cryptdin-3 induces novel apical conductance (s) in Cl– secretory, including cystic fibrosis, epithelia by Merlin (2001)
10.1136/gut.47.2.215 / Gut / Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-γδ expression by Yeung (2000)

Dates

Type	When
Created	22 years, 5 months ago (March 11, 2003, 5:34 a.m.)
Deposited	1 year, 7 months ago (Jan. 8, 2024, 11:50 p.m.)
Indexed	2 months ago (July 3, 2025, 8:52 a.m.)
Issued	22 years, 8 months ago (Jan. 1, 2003)
Published	22 years, 8 months ago (Jan. 1, 2003)
Published Online	22 years, 8 months ago (Jan. 7, 2003)
Published Print	22 years, 8 months ago (Jan. 7, 2003)

Funders 0

None

BibTeX

@article{FAHLGREN_2003, title={Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis}, volume={131}, ISSN={1365-2249}, url={http://dx.doi.org/10.1046/j.1365-2249.2003.02035.x}, DOI={10.1046/j.1365-2249.2003.02035.x}, number={1}, journal={Clinical and Experimental Immunology}, publisher={Oxford University Press (OUP)}, author={FAHLGREN, A and HAMMARSTRÖM, S and DANIELSSON, Å and HAMMARSTRÖM, M-L}, year={2003}, month=jan, pages={90–101} }

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      "author": "Schroder",
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      "volume": "267",
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      "doi-asserted-by": "crossref",
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      "author": "Porter",
      "year": "1997",
      "journal-title": "Infect Immun"
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      "author": "Singh",
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      "first-page": "2740",
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      "first-page": "237",
      "DOI": "10.1016/S0378-1119(98)00480-6",
      "article-title": "Structure and mapping of the human \u03b2-defensin HBD-2 gene and its expression at sites of inflammation",
      "volume": "222",
      "author": "Liu",
      "year": "1998",
      "journal-title": "Gene"
    },
    {
      "key": "2022011222001427000_b24",
      "doi-asserted-by": "crossref",
      "first-page": "714",
      "DOI": "10.1165/ajrcmb.22.6.4023",
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