Bacteroides fragilis enterotoxin upregulates heme oxygenase-1 in dendritic cells via reactive oxygen species-, mitogen-activated protein kinase-, and Nrf2-dependent pathway.
World J Gastroenterol
; 26(3): 291-306, 2020 Jan 21.
Article
em En
| MEDLINE
| ID: mdl-31988590
ABSTRACT
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-κB, AP-1, and Nrf2, activation of NF-κB 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
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Células Dendríticas
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Metaloendopeptidases
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Transdução de Sinais
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Enterotoxinas
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Heme Oxigenase-1
Limite:
Animals
Idioma:
En
Revista:
World J Gastroenterol
Ano de publicação:
2020
Tipo de documento:
Article