PDF《LPS and HIV gp120 modulate》

European Review for Medical and Pharmacological Sciences Abstract.

C 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-in- fected Italian patients. PATIENTS AND METHODS: We studied in a cohort of

91 HIV-infected Italian patients the me- tabolism 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 defi- ciency (25OHD <

10 ng/ml) and vitamin D insuffi- ciency (25OHD 10-30 ng/ml) was 31% and 57%, respectively. In univariate analysis, female sex (p = 0.01), increasing age (p = 0.05), higher high- ly 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 associa- tion 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 ?g/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. LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression leading to vitamin D consumption and hypovitaminosis D in HIV-infected individuals M.R. PINZONE1 , M. DI ROSA1 , B.M. CELESIA1 , F . CONDORELLI2 , M. MALAGUARNERA3 , G. MADEDDU4 , F . MARTELLOTTA5 , D. CASTRONUOVO1 , M. GUSSIO1 , C. COCO1 , F . PALERMO1 , S. COSENTINO1 , B. CACOPARDO1 , G. NUNNARI1,6

1 Department of Clinical and Molecular Biomedicine, Division of Infectious Diseases, University of Catania, Catania, Italy

2 DiSCAFF &

DFB Center, University of Piemonte Orientale A. Avogadro, Novara, Italy

3 International PhD programme in Neuropharmacology, University of Catania, Catania, Italy

4 Department of Clinical, Experimental and Oncological Medicine, Division of Infectious Diseases, University of Sassari, Sassari, Italy

5 Department of Medical Oncology, National Cancer Institute, Aviano Italy

6 Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, USA Corresponding Author: Giuseppe Nunnari, MD, Ph.D, MPH;

e-mail: [email protected] When monocytes were cultured in the pres- ence 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 pa- tients. Chronic inflammation, including residual viral replication, may contribute to hypovita- minosis D, by modulating vitamin D metabolism and catabolism. Systematic screening may help identifying subjects requiring supplementation. Key Words: Vitamin D deficiency, Vitamin D receptor, Parathor- mone, HIV-infected patients, gp 120, lipopolysaccha- ride. Introduction Even though highly active antiretroviral thera- py (HAART) has significantly changed the course of Human immunodeficiency virus (HIV) infection, it is not able to eradicate HIV infection1 . HIV persistence in latent reservoirs represents a major barrier to curing HIV2-12 . HIV infection is characterized by chronic inflamma- tion and immune activation. These factors have been shown to significantly contribute to the in- 2013;