Vitamin K deficiency leads to exacerbation of murine dextran sulfate sodium-induced colitis (Shiraishi E, et al)
Inflammatory bowel disease (IBD) comprises chronic relapsing and remitting disorders of the digestive tract, including Crohn’s disease (CD) and ulcerative colitis (UC). Although the pathophysiology of IBD has yet to be determined, recent studies have suggested that IBD is induced by impaired homeostasis of innate or adaptiveimmune responses in the intestine.
Patients with inflammatory bowel disease (IBD) often exhibit vitamin K deficiency. Metabolic bone diseases, including osteopenia and osteoporosis, are frequently associated with IBD. Insufficient vitamin K can cause diminished bone metabolism in non-IBD populations. 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.
Colitis was induced using dextran sulfate sodium (DSS) in mice fed either a vitamin K-deficient (Kdef) 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.
The results showed 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.
The researchers concluded that vitamin K exerts a protective effect against DSS colitis; this effect is associated with IL-6 downregulation. Therefore, vitamin K could be a potential treatment target for IBD.
Reference:
Shiraishi E, Iijima Ha, Shinzaki S, Nakajima S, Inoue T, Hiyama S, Kawai S, Araki M, Yamaguchi T, Hayashi Y, Fujii H, Nishida T, Tsujii M, Takehara T. Vitamin K deficiency leads to exacerbation of murine dextran sulfate sodium-induced colitis. J Gastroenterol. 2015 Aug 28. [Epub ahead of print]