Helicobacter pyloriInduces Increased Expression of the Vitamin D Receptor in Immune Responses

Autor: Yu Chen, Chaohui Yu, Wenguo Chen, Xingyong Wan, Shuhua Xu, Hua-Tuo Zhu, Lihua Chen, Ningmin Yang, Lihua Guo
Rok vydání: 2013
Předmět:
Zdroj: Helicobacter. 19:37-47
ISSN: 1083-4389
Popis: 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. Materials and 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 1a,25(OH)2D3 (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 1a,25(OH)2D3 increased CAMP expression and reduced cytokine activation in GES-1 cells infected with H. pylori .1 a,25(OH)2D3 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.
Databáze: OpenAIRE