LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression leading to vitamin D consumption and hypovitaminosis D in HIV-infected individuals

Eur Rev Med Pharmacol Sci. 2013 Jul;17(14):1938-50.

Abstract

Aim: 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.

Patients and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D 2 / metabolism
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / biosynthesis*
  • Adult
  • Cells, Cultured
  • DNA Primers
  • Female
  • HIV Envelope Protein gp120 / pharmacology*
  • HIV Infections / enzymology*
  • Humans
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects
  • Macrophages / enzymology*
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / enzymology*
  • Multivariate Analysis
  • Real-Time Polymerase Chain Reaction
  • Steroid Hydroxylases / metabolism*
  • Vitamin D / metabolism*
  • Vitamin D Deficiency / etiology*
  • Vitamin D3 24-Hydroxylase

Substances

  • DNA Primers
  • HIV Envelope Protein gp120
  • Interleukin-6
  • Lipopolysaccharides
  • Vitamin D
  • 25-Hydroxyvitamin D 2
  • Steroid Hydroxylases
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase