Cytochrome P450 Vitamin D Hydroxylases in Inflammation and Cancer

Abstract

Vitamin D insufficiency correlates with increased incidence of inflammatory disorders and cancer of the colon, breast, liver, and prostate. Preclinical studies demonstrated that the hormonally active form of vitamin D, 1,25(OH)2D3, has antiproliferative, proapoptotic, anti-inflammatory, and immunomodulatory effects. Tissue levels of 1,25(OH)2D3 are determined by expression and activity of specific vitamin D hydroxylases expressed at renal and extrarenal sites. In order to understand how perturbations in the vitamin D system affect human health, we need to understand the steps involved in the synthesis and catabolism of the active metabolite. This review provides an overview about recent findings on the altered vitamin D metabolism in inflammatory conditions and carcinogenesis. We will summarize existing data on the pathophysiological regulation of vitamin D hydroxylases and outline the role of adequate levels of 1,25(OH)2D3 on tissue homeostasis.

Keywords: 1,25(OH)(2)D(3); 20(OH)D(3); 25(OH)D(3); Autoimmune diseases; CYP11A; CYP24A1; CYP27B1; CYP2R1; Calcitriol; Cancer; Chronic inflammation; Immune system; Inflammatory bowel disease; Vitamin D.