Inflammation fails to induce the vitamin D3 1α-hydroxylase. (135.13)

Abstract

Abstract The active form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH) 2D3], is largely produced by a renally expressed enzyme 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), we wanted to investigate the conditions that induce extrarenal 1α-hydroxylase expression. Expression of the 1α-hydroxylase in extrarenal tissues including the immune system has been reported. We did not detect β-galactosidase expression in LPS-stimulated BMDM, splenocytes, and peritoneal cells. Moreover, in vivo challenges of LPS, α-galactosylceramide, and Listeria monocytogenes showed no detectable β-galactosidase expression in lung, liver, spleen, and blood. Cyp27B1 expression has been reported in the colon of both DSS-treated and control mice. Cyp27B1 KO mice were more susceptible to DSS colitis than WT mice and showed severe weight loss, inflammation, bleeding, and shrinkage of the colon. DSS treatment of Cyp27B1 KO mice resulted in spotty induction of β-galactosidase in the distal small intestine with a frequency of 3 positives for 22 tested and in the colon with a frequency of 6 positives for 22 tested. No β-galactosidase activity was detected in the intestines of untreated controls. The induction of Cyp27B1 expression was sporadic and not associated with the severity of disease. Our data does not support a role for the induction of Cyp27B1 following inflammation.