Vitamin D Synthesis Linked to Colitis in Mice
Mice lacking enzyme are more prone to colitis
WEDNESDAY, June 11 (HealthDay News) -- Levels of the enzyme that synthesizes vitamin D3, the active form of vitamin D important in immunity, are altered in the kidney and colon of a mouse model of colitis, and mice lacking the enzyme are more susceptible to colitis, according to a report published online June 5 in Endocrinology.
Nancy Liu, from the University of California Los Angeles, and colleagues examined the role of Cyp27b1, the enzyme that synthesizes 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), in a mouse model of colitis (induced by dextran sodium sulfate) and in mice lacking the Cyp27b1 gene.
The researchers found that mice with colitis weighed less, had increased production of inflammatory cytokines, had fivefold lower renal expression of Cyp27b1, had fourfold higher expression of Cyp27b1 in the proximal colon, and had reduced serum vitamin D3. Mice lacking the Cyp27b1 gene had significantly increased weight loss compared with mice having at least one copy of the gene, as well as colitis. This was associated with changes in interleukin-1 and interleukin-17 levels in the colon, while knockout mice induced to develop colitis had changes in the levels of interleukin-10 and toll-like receptors in the colon.
"These data indicate that both local and endocrine synthesis of 1,25(OH)2D3 affect colitis in dextran sodium sulfate-treated mice," Liu and colleagues conclude. "Lack of Cyp27b1 exacerbates disease in this model, suggesting that similar effects may occur with vitamin D deficiency."
One co-author is a consultant for DiaSorin Corp.