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

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Extra-renal 25-hydroxyvitamin D3-1α-hydroxylase in human health and disease. / Hewison, M; Burke, Fiona; Evans, K; Lammas, David; Sansom, David; Liu, P; Modlin, R; Adams, J.

In: The Journal of Steroid Biochemistry and Molecular Biology, Vol. 103, No. 3-5, 01.03.2007, p. 316-321.

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@article{e9c6adc3ad3b4343bfaef737f5262950,
title = "Extra-renal 25-hydroxyvitamin D3-1α-hydroxylase in human health and disease",
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.",
keywords = "tuberculosis, Crohn's disease, dendritic cell, granulomatous, extra-renal, 24-hydroxylase, macrophage, vitamin D, 1 alpha-hydroxylase, cancer",
author = "M Hewison and Fiona Burke and K Evans and David Lammas and David Sansom and P Liu and R Modlin and J Adams",
year = "2007",
month = mar,
day = "1",
doi = "10.1016/j.jsbmb.2006.12.078",
language = "English",
volume = "103",
pages = "316--321",
journal = "The Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier",
number = "3-5",

}

RIS

TY - JOUR

T1 - Extra-renal 25-hydroxyvitamin D3-1α-hydroxylase in human health and disease

AU - Hewison, M

AU - Burke, Fiona

AU - Evans, K

AU - Lammas, David

AU - Sansom, David

AU - Liu, P

AU - Modlin, R

AU - Adams, J

PY - 2007/3/1

Y1 - 2007/3/1

N2 - 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.

AB - 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.

KW - tuberculosis

KW - Crohn's disease

KW - dendritic cell

KW - granulomatous

KW - extra-renal

KW - 24-hydroxylase

KW - macrophage

KW - vitamin D

KW - 1 alpha-hydroxylase

KW - cancer

U2 - 10.1016/j.jsbmb.2006.12.078

DO - 10.1016/j.jsbmb.2006.12.078

M3 - Article

C2 - 17368179

VL - 103

SP - 316

EP - 321

JO - The Journal of Steroid Biochemistry and Molecular Biology

JF - The Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

IS - 3-5

ER -