Periparturient Diseases of Cattle Research Unit, National Animal Disease Center, Agricultural Research Service, USDA, Ames, IA 50010, USA.
J Dairy Sci. 2010 Mar;93(3):1041-9. doi: 10.3168/jds.2009-2663.
In cattle, the kidney has been the only known site for production of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] from 25-hydroxyvitamin D(3) [25(OH)D(3)] by 1alpha-hydroxylase (1alpha-OHase). Based on human studies, it was hypothesized that bovine monocytes could produce 1,25(OH)(2)D(3) upon activation and 1,25(OH)(2)D(3) would regulate expression of vitamin D-responsive genes in monocytes. First, the effects of 1,25(OH)(2)D(3) on bovine monocytes isolated from peripheral blood were tested. Treatment of nonstimulated monocytes with 1,25(OH)(2)D(3) increased expression of the gene for the vitamin D 24-hydroxylase (24-OHase) enzyme by 51+/-13 fold, but 1,25(OH)(2)D(3) induction of 24-OHase expression was blocked by lipopolysaccharide (LPS) stimulation. In addition, 1,25(OH)(2)D(3) increased the gene expression of inducible nitric oxide synthase and the chemokine RANTES (regulated upon activation, normal T-cell expressed and secreted) in LPS-stimulated monocytes 69+/-13 and 40+/-12 fold, respectively. Next, the ability of bovine monocytes to express 1alpha-OHase and produce 1,25(OH)(2)D(3) was tested. Activation of monocytes with LPS, tripalmitoylated lipopeptide (Pam3CSK4), or peptidoglycan caused 43+/-9, 17+/-3, and 19+/-3 fold increases in 1alpha-OHase gene expression, respectively. Addition of 25(OH)D(3) to LPS-stimulated monocytes enhanced expression of inducible nitric oxide synthase and RANTES and nitric oxide production in a dose-dependent manner, giving evidence that activated monocytes convert 25(OH)D(3) to 1,25(OH)(2)D(3). In conclusion, bovine monocytes produce 1,25(OH)(2)D(3) in response to toll-like receptor signaling, and 1,25(OH)(2)D(3) production in monocytes increased the expression of genes involved in the innate immune system. Vitamin D status of cattle might be important for optimal innate immune function because 1,25(OH)(2)D(3) production in activated monocytes and subsequent upregulation of inducible nitric oxide synthase and RANTES expression was dependent on 25(OH)D(3) availability.
在牛中，肾脏一直是已知的唯一能够将 25-羟维生素 D（3）[25（OH）D（3）]转化为 1α-羟化酶（1α-OHase）的 1,25-二羟维生素 D（3）[1,25（OH）（2）D（3）]的部位。基于人体研究，人们假设牛单核细胞在激活后可以产生 1,25（OH）（2）D（3），并且 1,25（OH）（2）D（3）将调节单核细胞中维生素 D 反应基因的表达。首先，测试了 1,25（OH）（2）D（3）对来自外周血的牛单核细胞的影响。用 1,25（OH）（2）D（3）处理未刺激的单核细胞，使维生素 D 24-羟化酶（24-OHase）基因的表达增加 51+/-13 倍，但脂多糖（LPS）刺激阻断了 1,25（OH）（2）D（3）诱导 24-OHase 表达。此外，1,25（OH）（2）D（3）分别使 LPS 刺激的单核细胞中诱导型一氧化氮合酶和趋化因子 RANTES（激活后正常 T 细胞表达和分泌）的基因表达增加 69+/-13 和 40+/-12 倍。接下来，测试了牛单核细胞表达 1α-羟化酶并产生 1,25（OH）（2）D（3）的能力。用 LPS、三棕榈酰化脂肽（Pam3CSK4）或肽聚糖激活单核细胞，分别使 1α-OHase 基因表达增加 43+/-9、17+/-3 和 19+/-3 倍。向 LPS 刺激的单核细胞中添加 25（OH）D（3）以剂量依赖性方式增强诱导型一氧化氮合酶和 RANTES 的表达并增加一氧化氮的产生，这表明激活的单核细胞将 25（OH）D（3）转化为 1,25（OH）（2）D（3）。总之，牛单核细胞对 Toll 样受体信号做出反应产生 1,25（OH）（2）D（3），而单核细胞中 1,25（OH）（2）D（3）的产生增加了参与固有免疫系统的基因的表达。牛的维生素 D 状态可能对最佳固有免疫功能很重要，因为激活的单核细胞中 1,25（OH）（2）D（3）的产生以及随后诱导型一氧化氮合酶和 RANTES 表达的上调都依赖于 25（OH）D（3）的可用性。
