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Cited by 474

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

NF-κB- and AP-1-Mediated Induction of Human Beta Defensin-2 in Intestinal Epithelial Cells by Escherichia coli Nissle 1917: a Novel Effect of a Probiotic Bacterium

Open access
Wehkamp, Jan, Harder, Jürgen, Wehkamp, Kai, Meissner, Birte Wehkamp-von, Schlee, Miriam, Enders, Corinne, Sonnenborn, Ulrich, Nuding, Sabine, Bengmark, Stig, Fellermann, Klaus, Schröder, Jens Michael, Stange, Eduard F.·2004·Infection and Immunity
DOI 10.1128/iai.72.10.5750-5758.2004
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Abstract

Little is known about the defensive mechanisms induced in epithelial cells by pathogenic versus probiotic bacteria. The aim of our study was to compare probiotic bacterial strains such as Escherichia coli Nissle 1917 with nonprobiotic, pathogenic and nonpathogenic bacteria with respect to innate defense mechanisms in the intestinal mucosal cell. Here we report that E. coli strain Nissle 1917 and a variety of other probiotic bacteria, including lactobacilli—in contrast to more than 40 different E. coli strains tested—strongly induce the expression of the antimicrobial peptide human beta-defensin-2 (hBD-2) in Caco-2 intestinal epithelial cells in a time- and dose-dependent manner. Induction of hBD-2 through E. coli Nissle 1917 was further confirmed by activation of the hBD-2 promoter and detection of the hBD-2 peptide in the culture supernatants of E. coli Nissle 1917-treated Caco-2 cells. Luciferase gene reporter analyses and site-directed mutagenesis experiments demonstrated that functional binding sites for NF-κB and AP-1 in the hBD-2 promoter are required for induction of hBD-2 through E. coli Nissle 1917. Treatment with the NF-κB inhibitor Helenalin, as well as with SP600125, a selective inhibitor of c-Jun N-terminal kinase, blocked hBD-2 induction by E. coli Nissle 1917 in Caco-2 cells. SB 202190, a specific p38 mitogen-activated protein kinase inhibitor, and PD 98059, a selective inhibitor of extracellular signal-regulated kinase 1/2, were ineffective. This report demonstrates that probiotic bacteria may stimulate the intestinal innate defense through the upregulation of inducible antimicrobial peptides such as hBD-2. The induction of hBD-2 may contribute to an enhanced mucosal barrier to the luminal bacteria.

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Metadata

Authors
Wehkamp, J., Harder, J., Wehkamp, K., Meissner, B. W.-V., Schlee, M., Enders, C., Sonnenborn, U., Nuding, S., Bengmark, S., Fellermann, K., Schröder, J. M., & Stange, E. F.
Venue
Infection and Immunity
Publisher
American Society for Microbiology
Published
2004-10
Volume
72
Issue
10
Pages
5750-5758
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
DOI
10.1128/iai.72.10.5750-5758.2004
OpenAlex
W2158364865
Cited by
474
References
3
FWCI
45.59
Type
journal article
Language
en
Open access
green

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