Premium
Toll‐like receptor signaling increases production of 1,25‐dihydroxyvitamin D3 in bovine macrophages
Author(s) -
Nelson Corwin D.,
Beitz Donald C.,
Reinhardt Tim A.,
Lippolis John D.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.672.28
Subject(s) - calcitriol receptor , cyp24a1 , tlr2 , receptor , vitamin d and neurology , tlr4 , chemistry , autocrine signalling , medicine , endocrinology , microbiology and biotechnology , biology , biochemistry
Activation of macrophages can occur through Toll‐like receptor (TLR) recognition of pathogen associated molecular patterns (PAMP). Recently, it has been discovered that TLR signaling can increase 1α‐hydroxylase (Cyp27B1) expression in human and mouse macrophages. The enzymatic activity of 1α‐hydroxylase produces the steroid hormone 1,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) from its precursor 25‐hydroxyvitamin D 3 (25(OH)D 3 . Thus, we hypothesized that TLR recognition of PAMP can increase Cyp27B1 expression and conversion of 25(OH)D 3 to 1,25(OH) 2 D 3 in bovine macrophages. We supplemented bovine monocyte derived macrophages (BMDM) with 25(OH)D 3 and stimulated them with ligands for TLR2 and TLR4. Quantitative real‐time PCR was used to measure changes in Cyp27B1 and 24‐hydroxylase (Cyp24A1) mRNA expression. Stimulation of BMDM with TLR2 and TLR4 ligands in the presence of 25(OH)D 3 resulted in increased Cyp27B1 and Cyp24A1 mRNA expression. Conversion of 25(OH)D 3 to 1,25(OH) 2 D 3 in BMDM was demonstrated by increased expression of Cyp24A1, which is dependent on binding of the vitamin D receptor/1,25(OH) 2 D 3 complex to the Cyp24A1 promoter. In conclusion, our results show that an autocrine vitamin D signaling pathway is present in bovine macrophages. Future studies will focus on the impact of vitamin D on the bovine immune system at the cellular and molecular level. Funded by USDA‐ARS CRIS 3625‐32000‐094‐00D