The Orosomucoid 1 protein is involved in the vitamin D - mediated macrophage de-activation process

Abstract

Orosomucoid 1 (ORM1), also named Alpha 1 acid glycoprotein A (AGP-A), is an abundant plasma protein characterized by anti-inflammatory and immune-modulating properties. The present study was designed to identify a possible correlation between ORM1 and Vitamin D3 (1,25(OH)2D3), a hormone exerting a widespread effect on cell proliferation, differentiation and regulation of the immune system. In particular, the data described here indicated that ORM1 is a 1,25(OH)2D3 primary response gene, characterized by the presence of a VDRE element inside the 1kb sequence of its proximal promoter region. This finding was demonstrated with gene expression studies, Chromatin Immunoprecipitation and luciferase transactivation experiments and confirmed by VDR full length and dominant negative over-expression. In addition, several experiments carried out in human normal monocytes demonstrated that the 1,25(OH)2D3--VDR--ORM1 pathway plays a functional role inside the macrophage de-activation process and that ORM1 may be considered as a signaling molecule involved in the maintenance of tissue homeostasis and remodeling.

Keywords: 1,25(OH)2D3; 1α, 25 dihydroxyvitamin D3; AF2; AGP-A; AKNA1; AT-Hook Transcription Factor 1; Activation function domain 2; Alpha 1 acid glycoprotein A; Alpha-1-acid glycoprotein; CAMP; CB; COL27A1; Cathelicidin Antimicrobial Peptide; Collagen, Type XXVII, alpha-1; Cord Blood; Gene regulation; MMP9; MRC1; Mannose Receptor, C-type1; Matrix Metalloproteinase 9; Monocyte; ORM1; ORM2; Orosomucoid 1; Orosomucoid 2; QRT-PCR; Quantitative Real Time PCR; RT; Room Temperature; SLR; Signal Log Ratio; TF; TSS; Transcription Factor; Transcriptional Start Site; VDRE; Vitamin D; Vitamin D Responsive Element; siRNA; small interference RNA.