SCOPE: Vitamin Dis a critical molecule for the properly controlled activity of the immune system. In myeloid-derived cells, vitamin Dinduces the production of the antimicrobial and antitumor peptide cathelicidin. In this study, the mechanism of the entry of 25-hydroxycholecalciferol (25(OH)D) in myeloid-derived cells is explored.
METHODS AND RESULTS: Here, a novel regulatory pathway of vitamin Dbiology is described. Using a polyclonal antibody, two different chemical inhibitors, and a high-density lipoprotein as a competing ligand, it is demonstrated here that the 25(OH)D signaling pathway in myeloid cells depends on scavenger receptor class B type I (SR-B1). This effect is observed in the THP-1 monocytic cell line and in human primary monocytes. SR-B1 blockade abrogates the cellular uptake of 25(OH)D leading to a general shut down of the gene transcription program modulated by 25(OH)D. The results obtained at the transcriptional level are confirmed at the protein and functional level for CD14 in the THP-1 cell line.
CONCLUSION: In conclusion, SR-B1 plays a critical role in vitamin Dbiology, paving the way for novel therapeutic interventions.