2016OncotargetOpen access

Age, serum 25-hydroxyvitamin D and vitamin D receptor (VDR) expression and function in peripheral blood mononuclear cells

Laura A. Coleman, Margarita Mishina, Mark G. Thompson, Sarah Spencer, A. Reber, William G. Davis, Po-Yung Cheng, Edward A. Belongia, H. Keipp Talbot, Maria E. Sundaram, Marie R. Griffin, David K. Shay, Suryaprakash Sambhara

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// Laura A. Coleman 1,4,* , Margarita Mishina 2,* , Mark Thompson 3 , Sarah M. Spencer 2 , Adrian J. Reber 3 , William G. Davis 3 , Po-Yung Cheng 3 , Edward A. Belongia 4 , H. Keipp Talbot 5 , Maria E. Sundaram 4,6 , Marie R. Griffin 5 , David K. Shay 3 and Suryaprakash Sambhara 3 1 Abbott Nutrition, Columbus, OH, USA 2 Battelle, Columbus, OH, USA 3 U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA 4 Marshfield Clinic, Marshfield, WI, USA 5 Vanderbilt University, Nashville, TN, USA 6 University of Minnesota School of Public Health, Minneapolis, MN, USA * These authors have contributed equally to this work Correspondence to: Laura A. Coleman, email: // Keywords : vitamin D, vitamin D receptor, 1α-hydroxylase, mRNA expression, PBMC, Gerotarget Received : March 06, 2016 Accepted : April 27, 2016 Published : May 17, 2016 Abstract The relationship between age, vitamin D status, expression and functionality of the vitamin D receptor (VDR), and key genes in the vitamin D pathway in immune cells is unclear. We enrolled adults 50 to 69 years old (20 subjects) and 70+ (20 subjects) and measured: 1) 25(OH)D levels by liquid chromatography/mass spectrometry; and 2) mRNA expression of VDR, 1α-OHase, 1,25D 3 -MARRS, TREM-1, cathelicidin, RIG-I, and interferon-β by qRT-PCR. Mean serum 25(OH)D was 30 ± 4 ng/mL and was not associated with age. Baseline expression of VDR, 1α-OHase, 1,25D 3 -MARRS, TREM-1, and RIG-I also did not differ by age; IFN-β expression, however, was higher in the 70+ year old group. 25(OH)D 3 - and 1,25(OH) 2 D 3 -induced VDR, TREM-1 and cathelicidin expression were similar between age groups, as was LPS-induced expression of VDR and of 1α-OHase. Ligand-induced 1,25D 3 -MARRS expression was higher in subjects ≥ 70 years. Serum 25(OH)D was inversely associated with LPS-stimulated VDR expression and with baseline or vitamin D-induced TREM-1 expression, adjusting for age, self-rated health, and functional status. In healthy adults ≥ 50 years, the expression and functionality of the VDR, 1α-OHase and key vitamin D pathway genes were not consistently associated with age.

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// Laura A. Coleman 1,4,* , Margarita Mishina 2,* , Mark Thompson 3 , Sarah M. Spencer 2 , Adrian J. Reber 3 , William G. Davis 3 , Po-Yung Cheng 3 , Edward A. Belongia 4 , H. Keipp Talbot 5 , Maria E. Sundaram 4,6 , Marie R. Griffin 5 , David K. Shay 3 and Suryaprakash Sambhara 3 1 Abbott Nutrition, Columbus, OH, USA 2 Battelle, Columbus, OH, USA 3 U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA 4 Marshfield Clinic, Marshfield, WI, USA 5 Vanderbilt University, Nashville, TN, USA 6 University of Minnesota School of Public Health, Minneapolis, MN, USA * These authors have contributed equally to this work Correspondence to: Laura A. Coleman, email: // Keywords : vitamin D, vitamin D receptor, 1α-hydroxylase, mRNA expression, PBMC, Gerotarget Received : March 06, 2016 Accepted : April 27, 2016 Published : May 17, 2016 Abstract The relationship between age, vitamin D status, expression and functionality of the vitamin D receptor (VDR), and key genes in the vitamin D pathway in immune cells is unclear. We enrolled adults 50 to 69 years old (20 subjects) and 70+ (20 subjects) and measured: 1) 25(OH)D levels by liquid chromatography/mass spectrometry; and 2) mRNA expression of VDR, 1α-OHase, 1,25D 3 -MARRS, TREM-1, cathelicidin, RIG-I, and interferon-β by qRT-PCR. Mean serum 25(OH)D was 30 ± 4 ng/mL and was not associated with age. Baseline expression of VDR, 1α-OHase, 1,25D 3 -MARRS, TREM-1, and RIG-I also did not differ by age; IFN-β expression, however, was higher in the 70+ year old group. 25(OH)D 3 - and 1,25(OH) 2 D 3 -induced VDR, TREM-1 and cathelicidin expression were similar between age groups, as was LPS-induced expression of VDR and of 1α-OHase. Ligand-induced 1,25D 3 -MARRS expression was higher in subjects ≥ 70 years. Serum 25(OH)D was inversely associated with LPS-stimulated VDR expression and with baseline or vitamin D-induced TREM-1 expression, adjusting for age, self-rated health, and functional status. In healthy adults ≥ 50 years, the expression and functionality of the VDR, 1α-OHase and key vitamin D pathway genes were not consistently associated with age.

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// Laura A. Coleman 1,4,* , Margarita Mishina 2,* , Mark Thompson 3 , Sarah M. Spencer 2 , Adrian J. Reber 3 , William G. Davis 3 , Po-Yung Cheng 3 , Edward A. Belongia 4 , H. Keipp Talbot 5 , Maria E. Sundaram 4,6 , Marie R. Griffin 5 , David K. Shay 3 and Suryaprakash Sambhara 3 1 Abbott Nutrition, Columbus, OH, USA 2 Battelle, Columbus, OH, USA 3 U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA 4 Marshfield Clinic, Marshfield, WI, USA 5 Vanderbilt University, Nashville, TN, USA 6 University of Minnesota School of Public Health, Minneapolis, MN, USA * These authors have contributed equally to this work Correspondence to: Laura A. Coleman, email: // Keywords : vitamin D, vitamin D receptor, 1α-hydroxylase, mRNA expression, PBMC, Gerotarget Received : March 06, 2016 Accepted : April 27, 2016 Published : May 17, 2016 Abstract The relationship between age, vitamin D status, expression and functionality of the vitamin D receptor (VDR), and key genes in the vitamin D pathway in immune cells is unclear. We enrolled adults 50 to 69 years old (20 subjects) and 70+ (20 subjects) and measured: 1) 25(OH)D levels by liquid chromatography/mass spectrometry; and 2) mRNA expression of VDR, 1α-OHase, 1,25D 3 -MARRS, TREM-1, cathelicidin, RIG-I, and interferon-β by qRT-PCR. Mean serum 25(OH)D was 30 ± 4 ng/mL and was not associated with age. Baseline expression of VDR, 1α-OHase, 1,25D 3 -MARRS, TREM-1, and RIG-I also did not differ by age; IFN-β expression, however, was higher in the 70+ year old group. 25(OH)D 3 - and 1,25(OH) 2 D 3 -induced VDR, TREM-1 and cathelicidin expression were similar between age groups, as was LPS-induced expression of VDR and of 1α-OHase. Ligand-induced 1,25D 3 -MARRS expression was higher in subjects ≥ 70 years. Serum 25(OH)D was inversely associated with LPS-stimulated VDR expression and with baseline or vitamin D-induced TREM-1 expression, adjusting for age, self-rated health, and functional status. In healthy adults ≥ 50 years, the expression and functionality of the VDR, 1α-OHase and key vitamin D pathway genes were not consistently associated with age.

Key concepts: Calcitriol receptor, Vitamin D and neurology, Cathelicidin, Peripheral blood mononuclear cell, Internal medicine, Endocrinology, Medicine, Receptor

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