Bacteroides fragilis enterotoxin induces human beta-defensin-2 expression in intestinal epithelial cells via a mitogen-activated protein kinase/I kappaB kinase/NF-kappaB-dependent pathway.
Enterotoxigenic Bacteroides fragilis (ETBF) produces an approximately 20-kDa heat-labile enterotoxin (BFT) that plays an essential role in mucosal inflammation. Although spontaneous disappearance of ETBF infection is common, little information is available on regulated expression of antibacterial factors in response to BFT stimulation. This study investigates the role of BFT in human beta-defensin 2 (hBD-2) induction from intestinal epithelial cells. Stimulation of HT-29 and Caco-2 intestinal epithelial cell lines with BFT resulted in the induction of hBD-2. Activation of a reporter gene for hBD-2 was dependent on the presence of NF-kappaB binding sites. In contrast, suppression of AP-1 did not affect hBD-2 expression in BFT-stimulated cells. Inhibition of p38 mitogen-activated protein kinase (MAPK) using SB203580 and small interfering RNA (siRNA) transfection resulted in a significant reduction in BFT-induced I kappaB kinase (IKK)/NF-kappaB activation and hBD-2 expression. Our results suggest that a pathway including p38 MAPK, IKK, and NF-kappaB activation is required for hBD-2 induction in intestinal epithelial cells exposed to BFT, and may be involved in the host defense following infection with ETBF.
Department of Microbiology, Hanyang University College of Medicine, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Korea.
Young Mee
YM
Yoon
Jin Young
JY
Lee
Doyoung
D
Yoo
Young-Suk
YS
Sim
Young-Jeon
YJ
Kim
Yu-Kyoung
YK
Oh
Ju Seop
JS
Kang
Sunil
S
Kim
Joo Sung
JS
Kim
Jung Mogg
JM
Kim
D001441:Bacteroides fragilis / Q000276:immunology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism*; D023083:beta-Defensins / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C106641:DEFB4A protein, human; D016328:NF-kappa B; D023083:beta-Defensins; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D008666:Metalloendopeptidases; C091198:fragilysin