The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is synthesized by the 1α-hydroxylase, which is encoded by the Cyp27B1 gene. Using transgenic mice that have replaced the Cyp27B1 gene with the bacterial lacZ reporter gene (β-galactosidase), the inflammatory conditions that induce Cyp27B1 in the immune system were probed. A variety of stimuli including lipopolysaccharide, anti-CD3 or PMA/ionomycin were used to stimulate splenocytes and bone marrow derived macrophage in vitro. Only anti-CD3 stimulation resulted in a low induction of β-galactosidase activity in the spleen, indicating that T cells might be a source of Cyp27B1. In vivo, challenge with lipopolysaccharide, α-galactosylceramide, and Listeria monocytogenes failed to induce β-galactosidase activity outside of the kidneys. During more prolonged and severe inflammation there was staining in both the lungs and the gastrointestinal tract for β-galactosidase. Furthermore, wild-type reconstitution of the hematopoietic cell population in Cyp27B1 KO mice protected the mice from experimental colitis. T cell production of Cyp27B1 activity was shown to be from the CD8+ but not the CD4+ T cell population. CD8+ T cells expressed the reporter gene only after 48 h of stimulation. The data is consistent with a model where CD8+ T cells are activated to produce Cyp27B1 and 1,25(OH)2D3 that serves to turn off the local immune response.
Keywords: 1,25(OH)(2)D(3); 1,25-dihydroxyvitamin D(3); 25(OH)D(3); 25-hydroxyvitamin D(3); BM; BMDM; BW; Cyp; Cyp27B1; DKO; DSS; IBD; IFN; Inflammation; KO; LPS; PTH; SI; T cells; TLR; VDR; Vitamin D; WT; body weight; bone marrow; bone marrow derived macrophages; dextran sodium sulfate; double knockout; gal; galactosidase; inflammatory bowel disease; interferon; knockout; lipopolysaccharide; parathyroid hormone; small intestine; toll-like receptor; vitamin D receptor; wild-type.
© 2014.