Vitamin D signaling in the bovine immune system

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2010-01-01
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Nelson, Corwin
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Donald C. Beitz
John D. Lippolis
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Biochemistry, Biophysics and Molecular Biology

The Department of Biochemistry, Biophysics, and Molecular Biology was founded to give students an understanding of life principles through the understanding of chemical and physical principles. Among these principles are frontiers of biotechnology such as metabolic networking, the structure of hormones and proteins, genomics, and the like.

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The Department of Biochemistry and Biophysics was founded in 1959, and was administered by the College of Sciences and Humanities (later, College of Liberal Arts & Sciences). In 1979 it became co-administered by the Department of Agriculture (later, College of Agriculture and Life Sciences). In 1998 its name changed to the Department of Biochemistry, Biophysics, and Molecular Biology.

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1959–present

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  • Department of Biochemistry and Biophysics (1959–1998)

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Biochemistry, Biophysics and Molecular Biology
Abstract

Vitamin D has predominantly been associated with calcium homeostasis, but recently been associated with several infectious diseases. The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is known to regulate the expression of numerous genes throughout the body. 1,25(OH)2D3 is synthesized from 25-hydroxyvitamin D3 by the enzyme 1α-hydroxylase (1α-OHase; CYP27B1). In the endocrine system, 1α-OHase expression, and subsequently 1,25(OH)2D3 synthesis, is tightly regulated in the kidney in response to calcium homeostasis. 1,25(OH)2D3 produced in the kidney acts systemically to regulate the expression of genes related to calcium homeostasis. In contrast, we have found that bovine monocytes (precursors to macrophages) express 1α-OHase upon activation by toll-like receptor recognition of pathogen associated molecular patterns. Furthermore, we found that 1α-OHase is highly expressed in CD14+ cells (monocytes and macrophages) from peripheral blood mononuclear cell cultures stimulated with a purified protein derivative of Mycobacteria bovis and from the infected mammary glands of cows with mastitis. Production of 1,25(OH)2D3 by 1α-OHase in bovine monocytes up-regulated the expression of the genes for iNOS and the chemokine RANTES in monocytes. Up-regulation of iNOS resulted in increased production of nitric oxide, a molecule that is considered to have several important roles in immune function. In stimulated peripheral blood mononuclear cell cultures, IFN-γ, IL-17A, and IL-17F, pro-inflammatory cytokines associated with T-cells, were down-regulated by 1,25(OH)2D3 that was presumably produced by monocytes. Finally, regulation of gene expression by 1,25(OH)2D3 produced by 1α-OHase in monocytes depended on the concentration of 25(OH)D3. The circulating concentration of 25(OH)D3 is controlled by dietary intake of vitamin D3 and sunlight exposure, so dietary intake of vitamin D3 and sunlight exposure may impact immune function in cattle. Current requirements for vitamin D in cattle are based on the regulation of calcium homeostasis, but those requirements may be inadequate for proper immune function. Therefore, further investigation is needed to determine vitamin D requirements for proper immune function in cattle.

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Fri Jan 01 00:00:00 UTC 2010