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Scavenger Receptor Class B Type I is Required for 25‐Hydroxycholecalciferol Cellular Uptake and Signaling in Myeloid Cells
Author(s) -
Tenesaca Shirley,
Vasquez Marcos,
FernandezSendin Myriam,
Di Trani Claudia Augusta,
Ardaiz Nuria,
Gomar Celia,
Cuculescu Doina,
Alvarez Maite,
Otano Itziar,
Melero Ignacio,
Berraondo Pedro
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201901213
Subject(s) - scavenger receptor , calcitriol receptor , myeloid , microbiology and biotechnology , cd14 , biology , immune system , chemistry , cathelicidin , receptor , signal transduction , biochemistry , lipoprotein , cancer research , immunology , cholesterol , innate immune system
Scope Vitamin D 3 is a critical molecule for the properly controlled activity of the immune system. In myeloid‐derived cells, vitamin D 3 induces 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 D 3 biology 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 D 3 biology, paving the way for novel therapeutic interventions.