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.
Helicobacter. 2014 Feb;19(1):37-47. doi: 10.1111/hel.12102. Epub 2013 Nov 4.
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 (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.
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.
维生素 D 受体（VDR）是核受体家族转录因子的成员，在先天免疫中发挥着关键作用。本研究探讨了 VDR 在胃固有免疫防御对抗胃病原体幽门螺杆菌中的作用。
17 例 H. pylori 感染患者和 16 例对照者参与了本研究。GES-1 细胞用 siRNA 转染或用或不用 1α,25(OH)2 D3（100 nmol/L）孵育，然后感染 H. pylori。通过 qRT-PCR 测定正常和 H. pylori 感染胃黏膜和 GES-1 细胞中 VDR、抗菌肽（CAMP）和细胞因子 mRNA 表达水平，并与胃炎的组织病理学程度相关。通过集落形成单位测定法测量杀菌活性。
H. pylori 感染患者的 VDR mRNA 表达水平显著上调，并与慢性炎症评分呈正相关。H. pylori 阳性胃黏膜中 VDR 和 CAMP mRNA 表达呈显著正相关。VDR siRNA 降低了 H. pylori 诱导的 CAMP 产生，相反增加了 IL-6 和 IL8/CXCL8 的表达水平。维生素 D 激动剂 1α,25(OH)2 D3 增加了 GES-1 细胞感染 H. pylori 时的 CAMP 表达，并减少了细胞因子的激活。1α,25(OH)2 D3 可以增强复制细菌的细胞内杀伤，但 siVDR 和 siCAMP 的存在导致其杀菌能力下降。
H. pylori 感染时胃上皮细胞中 VDR 和 CAMP 的表达上调；因此，VDR 在胃黏膜稳态和宿主保护免受 H. pylori 感染中发挥重要作用。
