Modulation of host antimicrobial peptide (beta-defensins 1 and 2) expression during gastritis

Bajaj-Elliott, Mona; Fedeli, P; Smith, Geoff; Domizio, P.; Maher, Louise; Ali, R S; Quinn, Anthony G.; Farthing, M J G

doi:10.1136/gut.51.3.356

Cited by 98 publications

(78 citation statements)

References 32 publications

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“…The best studied of these molecules are the defensins, which are a family of antimicrobial peptides that are expressed in neutrophils and on mucosal surfaces, where they are thought to play an important role in innate host defense (11). Recent evidence from cell culture experiments and gastric biopsies of chronically infected humans supports our finding that hBD-2 is induced by H. pylori and can inhibit its growth at concentrations as low as 10 Ϫ5 mol/l (6,41,92,95). Protease inhibitor 3 (elafin) is a defensin-like protein with a clear antimicrobial role in innate immune defense in the lung (78).…”

Section: Resultssupporting

confidence: 53%

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

2004

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Infection with Helicobacter pylori is usually asymptomatic but sometimes progresses to peptic ulcer disease or gastric adenocarcinoma. The development of disease involves both host and bacterial factors. In order to better understand host factors in pathogenesis, we studied the gastric transcription profile of H. pylori infection in the rhesus macaque by using DNA microarrays. Significant changes were found in the expression of genes important for innate immunity, chemokines and cytokines, cell growth and differentiation, apoptosis, structural proteins, and signal transduction and transcription factors. This broad transcription profile demonstrated expected up-regulation of cell structural elements and the host inflammatory and immune response, as well as the novel finding of down-regulation of heat shock proteins. These results provide a unique view of acute H. pylori infection in a relevant animal model system and will direct future studies regarding the host response to H. pylori infection.

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Section: Resultssupporting

confidence: 53%

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

2004

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“…In agreement with this result, BD2 mRNA expression was higher in the gastric mucosa of patients infected with cagA-positive strains than in that of patients infected with cagA-negative strains, a finding suggesting cag PAI-dependent induction of this peptide. BD2 was shown to be induced in the gastric epithelial tissues during H. pylori infection (37). Furthermore, cag PAI-dependent induction of BD2 was also observed in MKN45 cells infected with H. pylori (38).…”

Section: Discussionmentioning

confidence: 85%

Chemokines and Antimicrobial Peptides Have a cag -Dependent Early Response to Helicobacter pylori Infection in Primary Human Gastric Epithelial Cells

et al. 2014

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e Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-␣). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128⌬cagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection.

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“…Isogenic cagA mutant was isolated by transformation followed by allelic exchange and identity confirmed by Southern blotting. For co-culture experiments, both wild-type and isogenic bacterial strains were used at a multiplicity of infection of 100 (38).…”

Section: Methodsmentioning

confidence: 99%

Nucleotide-binding Oligomerization Domain-1 and Epidermal Growth Factor Receptor

Boughan¹,

Argent

Body-Malapel

et al. 2006

Journal of Biological Chemistry

159

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Host-pathogen interactions that allow Helicobacter pylori to survive and persist in the stomach of susceptible individuals remain unclear. Human ␤-defensins (hBDs), epithelial-derived antimicrobial peptides are critical components of host-defense at mucosal surfaces. The role of H. pylori-mediated NF-B and epidermal growth factor receptor (EGFR) activation on ␤-defensin expression was investigated. Transient transfection studies utilizing ␤-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 ␤-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.

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Modulation of host antimicrobial peptide (beta-defensins 1 and 2) expression during gastritis

Cited by 98 publications

References 32 publications

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

Gastric Transcription Profile of Helicobacter pylori Infection in the Rhesus Macaque

Chemokines and Antimicrobial Peptides Have a cag -Dependent Early Response to Helicobacter pylori Infection in Primary Human Gastric Epithelial Cells

Nucleotide-binding Oligomerization Domain-1 and Epidermal Growth Factor Receptor

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