Gut Liver.  2015 May;9(3):358-369. 10.5009/gnl13218.

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

• Kim BJ
• Kim JY
• Hwang ES
• Kim JG

• KMID: 2155644
• DOI: http://doi.org/10.5009/gnl13218

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.

Keyword

Nod1; Helicobacter pylori; cag pathogenicity island; Neutrophils; Transepithelial migration

MeSH Terms

Adult Stem Cells/physiology
Caco-2 Cells
Cell Line
Epithelial Cells/*metabolism/microbiology
Gene Expression
Genomic Islands
Helicobacter Infections/*genetics
*Helicobacter pylori
Humans
Interleukin-8/genetics/secretion
NF-kappa B/metabolism
Neutrophils/*physiology
Nod1 Signaling Adaptor Protein/*physiology
RNA, Messenger/metabolism
Signal Transduction
Transendothelial and Transepithelial Migration/*physiology
Up-Regulation
Interleukin-8
NF-kappa B
Nod1 Signaling Adaptor Protein
RNA, Messenger