title: Vitamin K deficiency leads to exacerbation of murine dextran sulfate sodium-induced colitis.
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.
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Eri
authors: E
authors: Shiraishi
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan. hiijima@gh.med.osaka-u.ac.jp.
authors: Hideki
authors: H
authors: Iijima
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Shinichiro
authors: S
authors: Shinzaki
authors: Division of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Japan.
authors: Sachiko
authors: S
authors: Nakajima
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Takahiro
authors: T
authors: Inoue
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Satoshi
authors: S
authors: Hiyama
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Shoichiro
authors: S
authors: Kawai
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Manabu
authors: M
authors: Araki
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Toshio
authors: T
authors: Yamaguchi
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Yoshito
authors: Y
authors: Hayashi
authors: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Hironobu
authors: H
authors: Fujii
authors: Division of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Japan.
authors: Tsutomu
authors: T
authors: Nishida
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Masahiko
authors: M
authors: Tsujii
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors: Tetsuo
authors: T
authors: Takehara
mesh_terms: D000818:Animals; D017209:Apoptosis; D003092:Colitis / Q000209:etiology / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D014813:Vitamin K Deficiency / Q000150:complications*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016264:Dextran Sulfate
keywords: B cells; IL-6; Inflammatory bowel disease; Vitamin K