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Critical Role of Vitamin D3 in Helicobacter pylori Eradication in Stomachs
Author(s) -
Hu Wei
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1067.6
Subject(s) - helicobacter pylori , cathelicidin , autophagy , microbiology and biotechnology , gastritis , medicine , biology , pharmacology , antimicrobial , antimicrobial peptides , biochemistry , apoptosis
Backgrounds and objectives Helicobacter pylori ( H. pylori ) establishes a new and important field in clinical microbiology, as the bacterium was found to be a major cause of several severe gastric disorders, including chronic gastritis and peptic ulcers. It is also a risk factor for adenocarcinoma and gastric lymphoma. Antibiotic treatment is adopted as the first therapeutic approach for H. pylori eradication. However, with the prevalence of antibiotics usage, multidrug resistance (MDR) is found to be increasingly common and also critical in clinics in the past decades. Therefore, new strategies of drug treatment are urgently needed for patients with H. pylori infection. This study aimed at demonstrating the critical role of vitamin D3 in H. pylori eradication. Methods PCR and immunostaning assay were used to determine the intracellular H. pylori level. Western blot assay was used to determine the autophagy‐related proteins level. Acridine Orange and GFP‐mCherry‐LC3 plasmid transfection were used to measure lysosomal acidification. Results We found a promising effect of vitamin D3 in clearing H. pylori infection both in gastric epithelial cells and in animals. The action was found to be independent on cathelicidin expression which was activated by vitamin D3 and shown to have anti‐bacterial action. Importantly, it was demonstrated that vitamin D3 could revitalize the degradation function of lysosomes which was adversely affected by H. pylori in cells after infection. This restoring effect was accomplished by lysosomal acidification enhancement. Moreover, we also found that the therapeutic action was not acting through vitamin D receptor, instead it was mediated by a separate receptor, the PDIA3 inside the cell, following by activating the calcium channel TRPML3 in lysosomes, and the degradation function can be restored by vitamin D3 through PDIA3 receptor. Conclusions Our studies revealed a novel and unique antibacterial pathway for Vitamin D3, which is different from the mechanisms of action for traditional antibiotics. Therefore, vitamin D3 could be a new therapeutic agent for bacterial infection and in particular those MDR bacteria in the future. Support or Funding Information This study was partly supported by the General Research Fund from the Hong Kong Research Grant Council (CUHK 463613) and the Health and Medical Research Fund from the Food and Health Bureau (13120062) in Hong Kong and the National Natural Science Foundation of China (No. 81473269).