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Nucleotide-binding oligomerization domain-1 and epidermal growth factor receptor - Critical regulators of beta-defensins during helicobacter pylori infection

Boughan, PK ; Argent, RH ; Body-Malapel, M ; Park, JH ; Ewings, KE ; Bowie, AG ; Ong, SJ ; Cook, SJ ; Sørensen, Ole E LU and Manzo, BA , et al. (2006) In Journal of Biological Chemistry 281(17). p.11637-11648
Abstract
Host-pathogen interactions that allow Helicobacter pylori to survive and persist in the stomach of susceptible individuals remain unclear. Human beta-defensins ( hBDs), epithelial-derived antimicrobial peptides are critical components of host-defense at mucosal surfaces. The role of H. pylori-mediated NF-kappa B and epidermal growth factor receptor ( EGFR) activation on beta-defensin expression was investigated. Transient transfection studies utilizing beta-defensin promoter constructs were conducted in gastric cells with contribution of individual signaling events evaluated by the addition of specific inhibitors, small interference nucleotide-binding oligomerization domain 1( NOD1) RNA or plasmids encoding Vaccinia virus proteins that... (More)
Host-pathogen interactions that allow Helicobacter pylori to survive and persist in the stomach of susceptible individuals remain unclear. Human beta-defensins ( hBDs), epithelial-derived antimicrobial peptides are critical components of host-defense at mucosal surfaces. The role of H. pylori-mediated NF-kappa B and epidermal growth factor receptor ( EGFR) activation on beta-defensin expression was investigated. Transient transfection studies utilizing beta-defensin promoter constructs were conducted in gastric cells with contribution of individual signaling events evaluated by the addition of specific inhibitors, small interference nucleotide-binding oligomerization domain 1( NOD1) RNA or plasmids encoding Vaccinia virus proteins that interrupt interleukin-1 and Toll-like receptor signaling. The role of individual MAPK pathways was further delineated in HEK-293 cells expressing conditional MAPK mutants. We found hBD2 expression exclusively dependent on the presence of the bacterial cag pathogenicity island, with NOD1 a critical host sensor. Impairment of murine beta-defensin 4( an orthologue of hBD2) expression in NOD1-deficient mice 7-days post-infection further confirmed the role of this cytoplasmic pattern-recognition receptor in eliciting host innate immunity. In contrast to hBD2, hBD3 expression was NOD1-independent but EGFR and ERK pathway-dependent. Importantly, Toll-like receptor signaling was not implicated in H. pylori-mediated hBD2 and hBD3 gene expression. The divergent signaling events governing hBD2 and hBD3 expression suggest temporal functional variation, such that hBD2 may contribute to antimicrobial barrier function during the inflammatory phase with hBD3 playing a greater role during the repair, wound healing phase of infection. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
281
issue
17
pages
11637 - 11648
publisher
ASBMB
external identifiers
  • wos:000236988100027
  • scopus:33744965671
ISSN
1083-351X
DOI
10.1074/jbc.M510275200
language
English
LU publication?
yes
id
56103d3e-c756-440c-999b-2798a50028c7 (old id 411171)
date added to LUP
2016-04-01 12:06:30
date last changed
2020-07-29 02:17:04
@article{56103d3e-c756-440c-999b-2798a50028c7,
  abstract     = {Host-pathogen interactions that allow Helicobacter pylori to survive and persist in the stomach of susceptible individuals remain unclear. Human beta-defensins ( hBDs), epithelial-derived antimicrobial peptides are critical components of host-defense at mucosal surfaces. The role of H. pylori-mediated NF-kappa B and epidermal growth factor receptor ( EGFR) activation on beta-defensin expression was investigated. Transient transfection studies utilizing beta-defensin promoter constructs were conducted in gastric cells with contribution of individual signaling events evaluated by the addition of specific inhibitors, small interference nucleotide-binding oligomerization domain 1( NOD1) RNA or plasmids encoding Vaccinia virus proteins that interrupt interleukin-1 and Toll-like receptor signaling. The role of individual MAPK pathways was further delineated in HEK-293 cells expressing conditional MAPK mutants. We found hBD2 expression exclusively dependent on the presence of the bacterial cag pathogenicity island, with NOD1 a critical host sensor. Impairment of murine beta-defensin 4( an orthologue of hBD2) expression in NOD1-deficient mice 7-days post-infection further confirmed the role of this cytoplasmic pattern-recognition receptor in eliciting host innate immunity. In contrast to hBD2, hBD3 expression was NOD1-independent but EGFR and ERK pathway-dependent. Importantly, Toll-like receptor signaling was not implicated in H. pylori-mediated hBD2 and hBD3 gene expression. The divergent signaling events governing hBD2 and hBD3 expression suggest temporal functional variation, such that hBD2 may contribute to antimicrobial barrier function during the inflammatory phase with hBD3 playing a greater role during the repair, wound healing phase of infection.},
  author       = {Boughan, PK and Argent, RH and Body-Malapel, M and Park, JH and Ewings, KE and Bowie, AG and Ong, SJ and Cook, SJ and Sørensen, Ole E and Manzo, BA and Inohara, N and Klein, NJ and Nunez, G and Atherton, JC and Bajaj-Elliott, M},
  issn         = {1083-351X},
  language     = {eng},
  number       = {17},
  pages        = {11637--11648},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Nucleotide-binding oligomerization domain-1 and epidermal growth factor receptor - Critical regulators of beta-defensins during helicobacter pylori infection},
  url          = {http://dx.doi.org/10.1074/jbc.M510275200},
  doi          = {10.1074/jbc.M510275200},
  volume       = {281},
  year         = {2006},
}