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Nucleotide Binding Oligomerization Domain 1 Is an Essential Signal Transducer in Human Epithelial Cells Infected with Helicobacter pylori That Induces the Transepithelial Migration of Neutrophils
Gut and Liver ; : 358-369, 2015.
Article in English | WPRIM | ID: wpr-203890
ABSTRACT
BACKGROUND/

AIMS:

The cytosolic host protein nucleotide binding oligomerization domain 1 (Nod1) has emerged as a key pathogen recognition molecule for innate immune responses in epithelial cells. The purpose of the study was to elucidate the mechanism by which Helicobacter pylori infection leads to transepithelial neutrophil migration in a Nod1-mediated manner.

METHODS:

Human epithelial cell lines AGS and Caco-2 were grown and infected with H. pylori. Interleukin (IL)-8 mRNA expression and IL-8 secretion were assessed, and nuclear factor kappaB (NF-kappaB) activation was determined. Stable transfections of AGS and Caco-2 cells with dominant negative Nod1 were generated. Neutrophil migration across the monolayer was quantified.

RESULTS:

Cytotoxin-associated gene pathogenicity island (cagPAI)(+) H. pylori infection upregulated IL-8 mRNA expression and IL-8 secretion in AGS and Caco-2 cells compared with controls. NF-kappaB activation, IL-8 mRNA expression and IL-8 secretion by cagPAI knockdown strains were reduced compared with those infected with the wild-type strain. NF-kappaB activation, IL-8 mRNA expression and IL-8 secretion in dominant-negative (DN)-Nod1 stably transfected cells were reduced compared with the controls. The transepithelial migration of neutrophils in DN-Nod1 stably transfected cells was reduced compared with that in controls.

CONCLUSIONS:

Signaling through Nod1 plays an essential role in neutrophil migration induced by the upregulated NF-kappaB activation and IL-8 expression in H. pylori-infected human epithelial cells.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: RNA, Messenger / Signal Transduction / Gene Expression / Up-Regulation / Cell Line / Interleukin-8 / NF-kappa B / Helicobacter pylori / Helicobacter Infections / Caco-2 Cells Limits: Humans Language: English Journal: Gut and Liver Year: 2015 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: RNA, Messenger / Signal Transduction / Gene Expression / Up-Regulation / Cell Line / Interleukin-8 / NF-kappa B / Helicobacter pylori / Helicobacter Infections / Caco-2 Cells Limits: Humans Language: English Journal: Gut and Liver Year: 2015 Type: Article