title: Helicobacter pylori induces increased expression of the vitamin d receptor in immune responses.
abstract: BACKGROUND
  Vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors that play a critical role in innate immunity. This study examined the role of VDR in gastric innate immune defence against the gastric pathogen Helicobacter pylori.
  
  
  METHODS
  Seventeen H. pylori-infected patients and sixteen controls participated in the study. The GES-1 cells were transfected with siRNA or incubated with or without 1α,25(OH)2 D3 (100 nmol/L) then infected with H. pylori. VDR, cathelicidin antimicrobial protein (CAMP), and cytokine mRNA expression levels in normal and H. pylori-infected gastric mucosa and GES-1 cells was determined by qRT-PCR and correlated with the histopathologic degree of gastritis. Bactericidal activity was measured by using a colony-forming unit assay.
  
  
  RESULTS
  Vitamin D receptor mRNA expression levels were significantly upregulated in H. pylori-infected patients and positively correlated with chronic inflammation scores. There was a significant positive correlation between VDR and CAMP mRNA expression in H. pylori-positive gastric mucosa. VDR siRNA reduced H. pylori-induced CAMP production and conversely increased IL-6 and IL8/CXCL8 expression levels. The vitamin D agonist 1α,25(OH)2 D3 increased CAMP expression and reduced cytokine activation in GES-1 cells infected with H. pylori. 1α,25(OH)2 D3 could enhance the intracellular killing of the replicating bacteria, but the presence of siVDR and siCAMP led to a decline in its bactericidal ability.
  
  
  CONCLUSIONS
  The expression of VDR and CAMP in the gastric epithelium is up-regulated in the case of H. pylori infection; thus, VDR plays an important role in gastric mucosa homeostasis and host protection from H. pylori infection.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China; Department of Gastroenterology, The Affiliated Hospital, College of Medicine, Ningbo University, Ningbo, 315020, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Guo
authors.forename: Wenguo
authors.initials: W
authors.lastname: Chen
authors.forename: Huatuo
authors.initials: H
authors.lastname: Zhu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Xingyong
authors.initials: X
authors.lastname: Wan
authors.forename: Ningmin
authors.initials: N
authors.lastname: Yang
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
authors.forename: Chaohui
authors.initials: C
authors.lastname: Yu
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000502:physiology*; D006651:Histocytochemistry; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol
keywords: 1α, 25(OH)2D3; H. pylori; cathelicidin; vitamin D receptor