Modulatory effects of the CCR5 antagonist maraviroc on microglial pro-inflammatory activation elicited by gp120

Lucia Lisi, Pierluigi Navarra, Cinzia Dello Russo, Antonella Tramutola, Andrea De Luca

Risultato della ricerca: Contributo in rivistaArticolo in rivista

27 Citazioni (Scopus)

Abstract

Despite important clinical benefits of the highly active antiretroviral therapy, neurological disorders affect approximately 50% of AIDS patients. In the brain, infected microglia release pro-inflammatory mediators as well as HIV-1 proteins, like the envolope protein gp120, that sustain inflammation and mediate neuronal damage. Gp120 allows the virus entry in the host cells via binding to the CD4 receptor together with a specific co-receptor (CCR5/CXCR4). The antiretroviral drug maraviroc is a CCR5 receptor antagonist, approved for the treatment of HIV-experienced patients. By interfering with a chemokine receptor, highly expressed in microglia, maraviroc has the potential to modulate their activation during HIV-1 infection. To test this hypothesis, primary cultures of rat cortical microglia were activated by gp120. Gp120CN54, a protein derived by macrophage (M)-tropic viruses, showed strong pro-inflammatory action, thus it was used to test the effects of maraviroc. The latter displayed opposite effects, depending on whether or not interferon-γ (IFNγ) was also present in the system. IFNγ significantly enhanced gp120 proinflammatory activity, possibly via upregulation of CCR5 receptor expression. In this experimental paradigm, maraviroc significantly increased microglial activation, thus suggesting that its chronic use can exacerbate neuronal pathology, especially in HIV-experienced patients with higher cerebral IFNγ levels.
Lingua originaleEnglish
pagine (da-a)106-114
Numero di pagine9
RivistaJournal of Neurochemistry
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • IFN gamma
  • gp120
  • maraviroc
  • microglia

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