ARS | Publication request: Autocrine signaling mechanism of vitamin D in the bovine innate immune response

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: November 2, 2007
Publication Date: March 17, 2008
Citation: Nelson, C.D., Beitz, D.C., Reinhardt, T.A., Lippolis, J.D. 2008. Autocrine signaling mechanism of vitamin D in the bovine innate immune response [abstract]. 2008 American Dairy Science Association, American Society of Animal Science, Midwestern Section, Annual Meeting. p. 37.

Technical Abstract: Vitamin D is 25-hydroxylated in the liver to provide the precursor for renal production of the steroid hormone 1,25-dihydroxyvitamin D (1,25(OH)2D3) by 1alpha-hydroxylase. This highly regulated endocrine pathway is key to controlling many aspects of calcium homeostasis. In contrast to the hormone’s well characterized endocrine role in regulation of calcium homeostasis, 1,25(OH) 2D3 has been found to be produced locally in activated macrophages. Activation of macrophages can occur through Toll-like receptor (TLR) recognition of pathogen associated molecular patterns (PAMP). Subsequently, the signal from TLR binding can increase local production of 1,25(OH) 2D3 by increasing expression of 1alpha-hydroxylase in human and mouse macrophages. Macrophage produced 1,25(OH) 2D3 has been shown to act locally to activate genes important for innate immune function in mice and humans. Thus, we hypothesized TLR recognition of PAMP can cause conversion of 25-hydroxyvitamin D3 to 1,25(OH) 2D3 by 1alpha-hydroxylase in bovine macrophages. Therefore, we stimulated bovine monocyte derived macrophages (BMDM) with ligands for TLR2 and TLR4 and measured expression of 1alpha-hydroxylase mRNA using quantitative real-time PCR (qPCR). Stimulation with the TLR2 and TLR4 ligands resulted in a 26-fold and 130-fold increase in 1alpha-hydroxylase mRNA expression, respectively. Increased production 1,25(OH) 2D3 in BMDM was then shown by 2.5 fold up-regulation of a VDRE dependent gene, 24-hydroxylase, in stimulated versus non-stimulated BMDM cultures. In conclusion, an autocrine signaling mechanism of vitamin D does occur in the bovine innate immune response. Future studies will need to examine the functional impact of 1,25(OH) 2D3 on the bovine immune system at the cellular and molecular level.