Document Detail


Enteric commensal bacteria induce extracellular signal-regulated kinase pathway signaling via formyl peptide receptor-dependent redox modulation of dual specific phosphatase 3.
MedLine Citation:
PMID:  21921027     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The normal microbial occupants of the mammalian intestine are crucial for maintaining gut homeostasis, yet the mechanisms by which intestinal cells perceive and respond to the microbiota are largely unknown. Intestinal epithelial contact with commensal bacteria and/or their products has been shown to activate noninflammatory signaling pathways, such as extracellular signal-related kinase (ERK), thus influencing homeostatic processes. We previously demonstrated that commensal bacteria stimulate ERK pathway activity via interaction with formyl peptide receptors (FPRs). In the current study, we expand on these findings and show that commensal bacteria initiate ERK signaling through rapid FPR-dependent reactive oxygen species (ROS) generation and subsequent modulation of MAP kinase phosphatase redox status. ROS generation induced by the commensal bacteria Lactobacillus rhamnosus GG and the FPR peptide ligand, N-formyl-Met-Leu-Phe, was abolished in the presence of selective inhibitors for G protein-coupled signaling and FPR ligand interaction. In addition, pretreatment of cells with inhibitors of ROS generation attenuated commensal bacteria-induced ERK signaling, indicating that ROS generation is required for ERK pathway activation. Bacterial colonization also led to oxidative inactivation of the redox-sensitive and ERK-specific phosphatase, DUSP3/VHR, and consequent stimulation of ERK pathway signaling. Together, these data demonstrate that commensal bacteria and their products activate ROS signaling in an FPR-dependent manner and define a mechanism by which cellular ROS influences the ERK pathway through a redox-sensitive regulatory circuit.
Authors:
Christy C Wentworth; Ashfaqul Alam; Rheinallt M Jones; Asma Nusrat; Andrew S Neish
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-31     Completed Date:  2012-01-09     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38448-55     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Proliferation
Dual Specificity Phosphatase 3 / metabolism*
Enterobacteriaceae / metabolism*
Epithelial Cells / metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism*
Gene Expression Regulation, Bacterial*
Humans
Intestines / microbiology*
Lactobacillus rhamnosus / metabolism
Mice
Mice, Inbred C57BL
Oxidation-Reduction*
Reactive Oxygen Species
Receptors, Formyl Peptide / metabolism*
Grant Support
ID/Acronym/Agency:
AI064462/AI/NIAID NIH HHS; DK089763/DK/NIDDK NIH HHS; K01DK081481/DK/NIDDK NIH HHS; R01 DK089763/DK/NIDDK NIH HHS; R01DK071604/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Receptors, Formyl Peptide; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.1.3.48/DUSP3 protein, human; EC 3.1.3.48/Dual Specificity Phosphatase 3; EC 3.1.3.48/Dusp3 protein, mouse
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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