Extra-renal 25-hydroxyvitamin D3-1α-hydroxylase in human health and disease

Research output: Contribution to journalArticle

Authors

  • M Hewison
  • K Evans
  • P Liu
  • R Modlin
  • J Adams

Colleges, School and Institutes

Abstract

Although ectopic expression of 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-OHase) has been recognized for many years, the precise function of this enzyme outside the kidney remains open to debate. Three specific aspects of extra-renal 1alpha-OHase have attracted most attention: (i) expression and regulation in non-classical tissues during normal physiology; (ii) effects on the immune system and inflammatory disease; (iii) expression and function in tumors. The most well-recognized manifestation of extra-renal 1alpha-OHase activity remains that found in some patients with granulomatous diseases where locally synthesized 1alpha,25(OH)(2)D(3) has the potential to spill-over into the general circulation. However, immunohistochemistry and mRNA analyses suggest that 1alpha-OHase is also expressed by a variety of normal human tissues including the gastrointestinal tract, skin, vasculature and placenta. This has promoted the idea that autocrine/paracrine synthesis of 1,25(OH)(2)D(3) contributes to normal physiology, particularly in mediating the potent effects of vitamin D on innate (macrophage) and acquired (dendritic cell) immunity. We have assessed the capacity for synthesis of 1,25(OH)(2)D(3) in these cells and the functional significance of autocrine responses to 1alpha-hydroxylase. Data suggest that local synthesis of 1,25(OH)(2)D(3) may be a preferred mode of response to antigenic challenge in many tissues.

Details

Original languageEnglish
Pages (from-to)316-321
Number of pages6
JournalThe Journal of Steroid Biochemistry and Molecular Biology
Volume103
Issue number3-5
Publication statusPublished - 1 Mar 2007

Keywords

  • tuberculosis, Crohn's disease, dendritic cell, granulomatous, extra-renal, 24-hydroxylase, macrophage, vitamin D, 1 alpha-hydroxylase, cancer