title: 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.
abstract: OBJECTIVE
  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 κB (NF-κB) 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-κB 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-κB 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-κB activation and IL-8 expression in H. pylori-infected human epithelial cells.
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.|Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Beom Jin
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Eung Soo
authors.initials: ES
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Jae Gyu
authors.initials: JG
authors.lastname: Kim
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology; D018938:Caco-2 Cells; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D015870:Gene Expression; D044404:Genomic Islands; D016481:Helicobacter Infections / Q000235:genetics*; D016480:Helicobacter pylori; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D053474:Nod1 Signaling Adaptor Protein / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; D012333:RNA, Messenger
keywords: Helicobacter pylori; Neutrophils; Nod1; Transepithelial migration; cag pathogenicity island