PMID- 31988590
OWN - NLM
STAT- MEDLINE
DCOM- 20201112
LR  - 20201112
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 26
IP  - 3
DP  - 2020 Jan 21
TI  - Bacteroides fragilis enterotoxin upregulates heme oxygenase-1 in dendritic cells 
      via reactive oxygen species-, mitogen-activated protein kinase-, and 
      Nrf2-dependent pathway.
PG  - 291-306
LID - 10.3748/wjg.v26.i3.291 [doi]
AB  - BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) causes colitis and 
      diarrhea, and is considered a candidate pathogen in inflammatory bowel diseases 
      as well as colorectal cancers. These diseases are dependent on ETBF-secreted 
      toxin (BFT). Dendritic cells (DCs) play an important role in directing the nature 
      of adaptive immune responses to bacterial infection and heme oxygenase-1 (HO-1) 
      is involved in the regulation of DC function. AIM: To investigate the role of BFT 
      in HO-1 expression in DCs. METHODS: Murine DCs were generated from specific 
      pathogen-free C57BL/6 and Nrf2(-/-) knockout mice. DCs were exposed to BFT, after 
      which HO-1 expression and the related signaling factor activation were measured 
      by quantitative RT-PCR, EMSA, fluorescent microscopy, immunoblot, and ELISA. 
      RESULTS: HO-1 expression was upregulated in DCs stimulated with BFT. Although BFT 
      activated transcription factors such as NF-kappaB, AP-1, and Nrf2, activation of 
      NF-kappaB and AP-1 was not involved in the induction of HO-1 expression in 
      BFT-exposed DCs. Instead, upregulation of HO-1 expression was dependent on Nrf2 
      activation in DCs. Moreover, HO-1 expression via Nrf2 in DCs was regulated by 
      mitogen-activated protein kinases such as ERK and p38. Furthermore, BFT enhanced 
      the production of reactive oxygen species (ROS) and inhibition of ROS production 
      resulted in a significant decrease of phospho-ERK, phospho-p38, Nrf2, and HO-1 
      expression. CONCLUSION: These results suggest that signaling pathways involving 
      ROS-mediated ERK and p38 mitogen-activated protein kinases-Nrf2 activation in DCs 
      are required for HO-1 induction during exposure to ETBF-produced BFT.
CI  - (c)The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Ko, Su Hyuk
AU  - Ko SH
AD  - Department of Microbiology and Department of Biomedical Science, Hanyang 
      University College of Medicine and Graduate School of Biomedical Science and 
      Engineering, Seoul 04763, South Korea.
FAU - Jeon, Jong Ik
AU  - Jeon JI
AD  - Department of Microbiology and Department of Biomedical Science, Hanyang 
      University College of Medicine and Graduate School of Biomedical Science and 
      Engineering, Seoul 04763, South Korea.
FAU - Woo, Hyun Ae
AU  - Woo HA
AD  - Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, 
      South Korea.
FAU - Kim, Jung Mogg
AU  - Kim JM
AD  - Department of Microbiology and Department of Biomedical Science, Hanyang 
      University College of Medicine and Graduate School of Biomedical Science and 
      Engineering, Seoul 04763, South Korea. jungmogg@hanyang.ac.kr.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Bacterial Toxins)
RN  - 0 (Enterotoxins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.- (Bacteroides fragilis toxin)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Animals
MH  - Bacterial Toxins/*immunology
MH  - Dendritic Cells/*immunology/microbiology
MH  - Enterotoxins/*immunology
MH  - Heme Oxygenase-1/*metabolism
MH  - Metalloendopeptidases/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*immunology
MH  - Up-Regulation
PMC - PMC6969884
OTO - NOTNLM
OT  - Bacteroides fragilis enterotoxin
OT  - Dendritic cells
OT  - Heme oxygenase-1
OT  - Mitogen-activated protein kinases
OT  - Nrf2
OT  - Signaling
COIS- Conflict-of-interest statement: None of the authors of this study has any 
      conflicts of interest.
EDAT- 2020/01/29 06:00
MHDA- 2020/11/13 06:00
PMCR- 2020/01/21
CRDT- 2020/01/29 06:00
PHST- 2019/10/28 00:00 [received]
PHST- 2019/12/20 00:00 [revised]
PHST- 2020/01/11 00:00 [accepted]
PHST- 2020/01/29 06:00 [entrez]
PHST- 2020/01/29 06:00 [pubmed]
PHST- 2020/11/13 06:00 [medline]
PHST- 2020/01/21 00:00 [pmc-release]
AID - 10.3748/wjg.v26.i3.291 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2020 Jan 21;26(3):291-306. doi: 10.3748/wjg.v26.i3.291.