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

Do Young Yoo, Su Hyuk Ko, Jireh Jung, Young Jeon Kim, Joo Sung Kim, Jung Mogg Kim

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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-κB 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.

Original languageEnglish (US)
Pages (from-to)384-396
Number of pages13
JournalLaboratory Investigation
Issue number4
StatePublished - Apr 2013
Externally publishedYes


  • AP-1
  • Bacteroides fragilis enterotoxin
  • intestinal epithelial cells
  • mitogen-activated protein kinase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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