Submitted to: Research Workers in Animal Diseases Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/30/2009
Publication Date: 12/6/2009
Citation: Nelson, C.D., Reinhardt, T.A., Beitz, D.C., Lippolis, J.D. 2009. Improvement of the Innate Immune Response of Bovine Monocytes Via an Intracrine Vitamin D Signaling Pathway [abstract]. Conference of Research Workers in Animal Diseases. Paper No. 94. Interpretive Summary:
Technical Abstract: Production of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) from 25-hydroxyvitamin D3 25(OH)D3 is accomplished by the enzyme 1alpha-hydroxylase (1alpha-OHase). In cattle, the kidney has been the only known site of 1,25(OH)2D3 synthesis. Production of 1,25(OH)2D3 in the kidney functions to maintain mineral homeostasis in an endocrine pathway by regulating gene expression systemically. However, we hypothesized that bovine monocytes could also produce 1,25(OH)2D3 upon activation and that 1,25(OH)2D3 modulates the innate immune response by regulating gene expression in monocytes via an intracrine pathway. The ability of bovine monocytes isolated from peripheral blood to express 1alpha-OHase in response to TLR signaling was tested and it was found that treatment with LPS, tripalmitoylated lipopeptide (Pam3CSK4), or peptidoglycan (PGN) increased 1alpha-OHase gene expression significantly. Treatment of stimulated monocytes with exogenous 1,25(OH)2D3 caused significant up-regulation of iNOS and RANTES gene expression. Nitric oxide production also increased as a result of 1,25(OH)2D3 induction of iNOS gene expression in stimulated monocytes. Addition of 25(OH)D3 to LPS-stimulated monocytes increased RANTES and iNOS gene expression in a dose dependent manner, showing that activated monocytes can convert 25(OH)D3 to 1,25(OH)2D3. In conclusion, an intracrine pathway of vitamin D signaling exists in bovine monocytes where 25(OH)D3 is converted to 1,25(OH)2D3 in response to TLR signaling. Production of 1,25(OH)2D3 in bovine monocytes increases RANTES and iNOS gene expression which may improve the antimicrobial and chemotactic properties of monocytes. Evidence from this study suggests that vitamin D status of cattle maybe important for optimal immune function and further investigation is needed to determine the vitamin D requirements for proper immune function in cattle.