title: Bacteroides fragilis enterotoxin upregulates lipocalin-2 expression in intestinal epithelial cells.
abstract: 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.
authors: Department of Microbiology, Hanyang University College of Medicine and Graduate School of Biomedical Science and Engineering, Seoul, Korea.
authors: Do Young
authors: do Y
authors: Yoo
authors: Su Hyuk
authors: SH
authors: Ko
authors: Jireh
authors: J
authors: Jung
authors: Young-Jeon
authors: YJ
authors: Kim
authors: Joo Sung
authors: JS
authors: Kim
authors: Jung Mogg
authors: JM
authors: Kim
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000633:toxicity*; D004847:Epithelial Cells / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008666:Metalloendopeptidases / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000209:Acute-Phase Proteins; D001427:Bacterial Toxins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D018808:Transcription Factor AP-1; C405031:Bacteroides fragilis toxin; D008666:Metalloendopeptidases