Helicobacter pylori Induces Increased Expression of the Vitamin D Receptor in Immune Responses

Abstract

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. 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 (100nmol/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. 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. 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.