title: 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.
authors: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena, Italy; Center for Regenerative Medicine, University of Modena and Reggio Emilia, Via Gottardi 100, 41125 Modena, Italy. Electronic address: claudia.gemelli@unimore.it.
authors: Claudia
authors: C
authors: Gemelli
authors: Andrea
authors: A
authors: Martello
authors: Monica
authors: M
authors: Montanari
authors: Tommaso
authors: T
authors: Zanocco Marani
authors: Valentina
authors: V
authors: Salsi
authors: Vincenzo
authors: V
authors: Zappavigna
authors: Sandra
authors: S
authors: Parenti
authors: Tatiana
authors: T
authors: Vignudelli
authors: Tommaso
authors: T
authors: Selmi
authors: Sergio
authors: S
authors: Ferrari
authors: Alexis
authors: A
authors: Grande
mesh_terms: D020869:Gene Expression Profiling; D018922:HL-60 Cells; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009961:Orosomucoid / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D020298:U937 Cells; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D009961:Orosomucoid; D014807:Vitamin D
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