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Journal of Gastroenterology
Published in: Journal of Gastroenterology 4/2016

01-04-2016 | Original Article—Alimentary Tract

Vitamin K deficiency leads to exacerbation of murine dextran sulfate sodium-induced colitis

Authors: Eri Shiraishi, Hideki Iijima, Shinichiro Shinzaki, Sachiko Nakajima, Takahiro Inoue, Satoshi Hiyama, Shoichiro Kawai, Manabu Araki, Toshio Yamaguchi, Yoshito Hayashi, Hironobu Fujii, Tsutomu Nishida, Masahiko Tsujii, Tetsuo Takehara

Published in: Journal of Gastroenterology | Issue 4/2016

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Abstract

Background

Patients with inflammatory bowel disease (IBD) often exhibit vitamin K deficiency. Vitamin K has been shown to inhibit inflammation via interleukin (IL)-6 suppression. This study aimed to evaluate the effect of vitamin K in a murine model of colitis.

Methods

Colitis was induced using dextran sulfate sodium (DSS) in mice fed either a vitamin K-deficient (K-def) or a vitamin K-supplemented (K-sup) diet. The clinical and histological severity of colitis was assessed, and levels of cytokine production from the spleen and colonic lamina propria were measured by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction. Cytokine expression levels in CD4+, CD11b+, and CD19+ cells in the presence and absence of vitamin K [menatetrenone (MK-4)] were measured in vitro and apoptosis was determined by caspase 3/7 activity and Annexin V staining.

Results

DSS administration resulted in significantly more severe body weight loss, shorter colon length, and higher histological scores in mice fed a K-def diet than those fed a K-sup diet. IL-6 expression in lamina propria mononuclear cells was significantly higher in the K-def group than in the K-sup group. IL-6 expression was significantly decreased in the presence of MK-4 in CD19+ cells, but not in the CD4+ and CD11b+ subpopulations. Apoptotic cell population in CD19+ cells was increased in the presence of MK-4 in vitro and in vivo.

Conclusions

Vitamin K exerts a protective effect against DSS colitis; this effect is associated with IL-6 downregulation. Vitamin K could be a potential treatment target for IBD.
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Metadata
Title
Vitamin K deficiency leads to exacerbation of murine dextran sulfate sodium-induced colitis
Authors
Eri Shiraishi
Hideki Iijima
Shinichiro Shinzaki
Sachiko Nakajima
Takahiro Inoue
Satoshi Hiyama
Shoichiro Kawai
Manabu Araki
Toshio Yamaguchi
Yoshito Hayashi
Hironobu Fujii
Tsutomu Nishida
Masahiko Tsujii
Tetsuo Takehara
Publication date
01-04-2016
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 4/2016
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-015-1112-x

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