Vitamin D3 Inhibits Helicobacter pylori Infection by Activating the VitD3/VDR-CAMP Pathway in Mice.

Anni Zhou,Shutian Zhang,Li Min,Lei Li,Shengtao Zhu,Si Liu,Guiping Zhao,Qingdong Guo,Chunjie Liu,Peng Li

doi:10.3389/fcimb.2020.566730

Abstract

Helicobacter pylori (H. pylori) infection is closely associated with the occurrence and development of gastric diseases. Therefore, eliminating H. pylori infection should help to prevent gastric diseases. Vitamin D3 (VitD3, 1,25(OH)2D3) was previously observed to exhibit anti-H. pylori infection activity in clinic, but these results were reported in heterogeneous in vivo studies without elucidation of the underlying mechanisms. In the present study, we established H. pylori infection models in both wild-type and VDR knockdown (VDR-KD) mice, which were used to demonstrate that VitD3 inhibits H. pylori infection by enhancing the expression of VitD receptor (VDR) and cathelicidin antimicrobial peptide (CAMP). Furthermore, VDR-KD mice that exhibited lower VDR expression were more susceptible to H. pylori infection. In cultured mouse primary gastric epithelial cells, we further demonstrated that the VitD3/VDR complex binds to the CAMP promoter region to increase its expression. These data provide a mechanistic explanation of the anti-H. pylori infection activity of VitD3 at the molecular level in mice and suggest a new avenue for the clinical management of H. pylori eradication therapy.

Highlights

Gastric diseases, including gastritis, gastric ulcers, and gastric cancer, are a serious threat to human health
Compared to that observed in the control mice (Figure 1A), large amounts of inflammatory cell infiltration and congestion were observed in the gastric mucosa of the infected mice (Figures 1B, C), indicating that chronic inflammation had occurred
These results demonstrate that the H. pylori infection mouse model was established

Summary

Introduction

Gastric diseases, including gastritis, gastric ulcers, and gastric cancer, are a serious threat to human health. According to a previous report (Bray et al, 2018), the incidence of gastric disease has markedly increased in recent years. According to the latest Global Cancer Statistics 2018 reports, the incidence and mortality associated with gastric cancer, which involves the development of malignant tumors, rank fifth and third worldwide, respectively, among all cancers. The pathogenesis of gastric disease is complex and remains largely unclear. Helicobacter pylori (H. pylori) infection is most often linked to the occurrence and development of gastric diseases (Tsukamoto et al, 2013)

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Results

Conclusion