Regulation of the extrarenal CYP27B1-hydroxylase.

Abstract

Provided here is a collective review of research on the extrarenal CYP27B1-hydroxylase that shapes our current and expanding vision of the role this enzyme plays in the intracrinology and paracrinology, as opposed to the traditional endocrinology, of vitamin D to regulate the innate and adaptive immune responses, particularly in human granuloma-forming diseases like tuberculosis. Special emphasis is placed on soluble factors (i.e., cytokines) in the local microenvironment of these human diseases that coordinate amplification and feedback inhibition of the macrophage CYP27B1-hydroxylase. Principal among these factors are Type I and Type II interferons (IFNs); the Type II IFN, IFN-γ, stimulates the production of 1,25-dihydroxyvitamin D (1,25(OH)2D) from 25-hydroxyvitamin D (25OHD) by the granuloma-forming disease-activated macrophage, while the Type I IFNs, IFN-α and IFN-β, block the hydroxylation reaction. The Type I IFN response is associated with more aggressive disease, while the Type II IFN response, the one that promotes 1,25(OH)2D production by the macrophage, is associated with more confined disease. Tilting the balance in the human immune response toward a confined disease phenotype is enabled by the presence of sufficient extracellular 25OHD to modulate IFN-γ-promoted and substrate 25OH-driven intracellular synthesis of 1,25(OH)2D. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

• Authors: John S Adams, Brandon Rafison, Sten Witzel, Rachel E Reyes, Albert Shieh, Rene Chun, Kathryn Zavala, Martin Hewison, Philip T Liu
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 144 Pt A Pg. 22-7 (Oct 2014) ISSN: 1879-1220 [Electronic] England
• PMID: 24388948 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Calcitriol
• Vitamin D
• 25-hydroxyvitamin D
• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Topics

• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (genetics, metabolism)
• Animals
• Gene Expression Regulation
• Humans
• Macrophages (enzymology)
• Receptors, Calcitriol (metabolism)
• Transcription, Genetic
• Vitamin D (analogs & derivatives, metabolism)