Bacteroides fragilis enterotoxin upregulates lipocalin-2 expression in intestinal epithelial cells

Enterotoxigenic Bacteroides fragilis (ETBF) produces an ∼20 kDa B. fragilis enterotoxin (BFT), which plays an essential role in mucosal inflammation. Lipocalin (Lcn)-2, a siderophore-binding antimicrobial protein, is critical for control of bacterial infection; however, expression of Lcn-2 in BFT-ex...

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Bibliographic Details
Published in:Laboratory investigation 2013-04, Vol.93 (4), p.384-396
Main Authors: Yoo, Do Young, Ko, Su Hyuk, Jung, Jireh, Kim, Young-Jeon, Kim, Joo Sung, Kim, Jung Mogg
Format: Article
Language:English
Subjects:
631/208/200
631/250/347
692/698/2741/278
692/699/255/1318
Acute-Phase Proteins - genetics
Acute-Phase Proteins - metabolism
Bacterial Toxins - toxicity
Bacteroides fragilis
Epithelial Cells - metabolism
HT29 Cells
Humans
Intestinal Mucosa - drug effects
Intestinal Mucosa - metabolism
Laboratory Medicine
Lipocalin-2
Lipocalins - genetics
Lipocalins - metabolism
MAP Kinase Signaling System
Medicine
Medicine & Public Health
Metalloendopeptidases - toxicity
NF-kappa B - metabolism
Pathology
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
research-article
Transcription Factor AP-1 - metabolism
Up-Regulation
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Summary:Enterotoxigenic Bacteroides fragilis (ETBF) produces an ∼20 kDa B. fragilis enterotoxin (BFT), which plays an essential role in mucosal inflammation. Lipocalin (Lcn)-2, a siderophore-binding antimicrobial protein, is critical for control of bacterial infection; however, expression of Lcn-2 in BFT-exposed intestinal epithelial cells has not been elucidated. In the present study, stimulation of human intestinal epithelial cells with BFT resulted in the upregulation of Lcn-2 expression that was a relatively late response of intestinal epithelial cells compared with human β -defensin (hBD)-2 expression. The upregulation of Lcn-2 was dependent on AP-1 but not on NF- κ B signaling. Lcn-2 induction via AP-1 was regulated by mitogen-activated protein kinases (MAPKs) including ERK and p38. Lcn-2 was secreted from the apical and basolateral surfaces in BFT-treated cells. These results suggest that a signaling pathway involving MAPKs and AP-1 is required for Lcn-2 induction in intestinal epithelial cells exposed to BFT, after which the secreted Lcn-2 may facilitate antimicrobial activity within ETBF-infected mucosa.
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.2013.1