title: HIV-1 infection is associated with changes in nuclear receptor transcriptome, pro-inflammatory and lipid profile of monocytes.
abstract: BACKGROUND
  Persistent residual immune activation and lipid dysmetabolism are characteristics of HIV positive patients receiving an highly active antiretroviral therapy (HAART). Nuclear Receptors are transcription factors involved in the regulation of immune and metabolic functions through the modulation of gene transcription. The objective of the present study was to investigate for the relative abundance of members of the nuclear receptor family in monocytic cells isolated from HIV positive patients treated or not treated with HAART.
  
  
  METHODS
  Monocytes isolated from peripheral blood mononuclear cells (PBMC) were used for analysis of the relative mRNA expressions of FXR, PXR, LXR, VDR, RARα, RXR, PPARα, PPARβ, PPARγ and GR by Real-Time polymerase chain reaction (PCR). The expression of a selected subset of inflammatory and metabolic genes MCP-1, ICAM-1, CD36 and ABCA1 was also measured.
  
  
  RESULTS
  Monocytes isolated from HIV infected patients expressed an altered pattern of nuclear receptors characterized by a profound reduction in the expressions of FXR, PXR, PPARα, GR, RARα and RXR. Of interest, the deregulated expression of nuclear receptors was not restored under HAART and was linked to an altered expression of genes which supports both an immune activation and altered lipid metabolism in monocytes.
  
  
  CONCLUSIONS
  Altered expression of genes mediating reciprocal regulation of lipid metabolism and immune function in monocytes occurs in HIV. The present findings provide a mechanistic explanation for immune activation and lipid dysmetabolism occurring in HIV infected patients and could lead to the identification of novel potential therapeutic targets.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Perugia, Perugia, Italy. barbara.renga@unipg.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Renga
authors.forename: Daniela
authors.initials: D
authors.lastname: Francisci
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Amore
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Schiaroli
authors.forename: Adriana
authors.initials: A
authors.lastname: Carino
authors.forename: Franco
authors.initials: F
authors.lastname: Baldelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D010865:Pilot Projects; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D059467:Transcriptome
chemical_list: D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear