title: LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression leading to vitamin D consumption and hypovitaminosis D in HIV-infected individuals.
abstract: OBJECTIVE
  Vitamin D deficiency is very common among HIV-infected subjects. We cross-sectionally evaluated the prevalence and risk factors for hypovitaminosis D in 91 HIV-infected Italian patients.
  
  
  METHODS
  We studied in a cohort of 91 HIV-infected Italian patients the metabolism of Vitamin D by evaluating the in vitro expression of CYP27B1, CYP24A1 and vitamin D receptor (VDR) by monocytes and macrophages stimulated with the viral envelope protein gp120 or lipopolysaccharide (LPS).
  
  
  RESULTS
  The prevalence of vitamin D deficiency (25OHD < 10 ng/ml) and vitamin D insufficiency (25OHD 10-30 ng/ml) was 31% and 57%, respectively. In univariate analysis, female sex (p = 0.01), increasing age (p = 0.05), higher highly sensitive-C reactive protein (p = 0.025), higher parathyroid hormone (PTH) (p = 0.043) and lower BMI (p = 0.04) were associated with vitamin D deficiency. In multivariate analysis, the association was still significant only for PTH (p = 0.03) and female sex (p = 0.03). Monocyte stimulation with LPS (100 ng/ml) or gp120 (1 µg/ml) significantly upregulated CYP27B1 mRNA expression. Moreover, gp120 significantly increased VDR mRNA levels. On the contrary, neither LPS nor gp120 modified CYP24A1 levels. Macrophage stimulation with LPS (100 ng/ml) significantly upregulated CYP27B1 and CYP24A1 mRNA expression. When monocytes were cultured in the presence of 25OHD (40 ng/ml) and stimulated with LPS we detected significantly lower levels of 25OHD in the supernatant.
  
  
  CONCLUSIONS
  Vitamin D deficiency was very common in our cohort of HIV-infected patients. Chronic inflammation, including residual viral replication, may contribute to hypovitaminosis D, by modulating vitamin D metabolism and catabolism. Systematic screening may help identifying subjects requiring supplementation.
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy. gnunnari@hotmail.com
authors.forename: M R
authors.initials: MR
authors.lastname: Pinzone
authors.forename: M
authors.initials: M
authors.lastname: Di Rosa
authors.forename: B M
authors.initials: BM
authors.lastname: Celesia
authors.forename: F
authors.initials: F
authors.lastname: Condorelli
authors.forename: M
authors.initials: M
authors.lastname: Malaguarnera
authors.forename: G
authors.initials: G
authors.lastname: Madeddu
authors.forename: F
authors.initials: F
authors.lastname: Martellotta
authors.forename: D
authors.initials: D
authors.lastname: Castronuovo
authors.forename: M
authors.initials: M
authors.lastname: Gussio
authors.forename: C
authors.initials: C
authors.lastname: Coco
authors.forename: F
authors.initials: F
authors.lastname: Palermo
authors.forename: S
authors.initials: S
authors.lastname: Cosentino
authors.forename: B
authors.initials: B
authors.lastname: Cacopardo
authors.forename: G
authors.initials: G
authors.lastname: Nunnari
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000378:metabolism; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis*; D000328:Adult; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015658:HIV Infections / Q000201:enzymology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D015999:Multivariate Analysis; D060888:Real-Time Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000209:etiology*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D017931:DNA Primers; D015699:HIV Envelope Protein gp120; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014807:Vitamin D; D015652:25-Hydroxyvitamin D 2; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase