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Related Experiment Videos

Anti-HIV drugs decrease the expression of matrix metalloproteinases in astrocytes and microglia.

G M Liuzzi1, C M Mastroianni, T Latronico

  • 1Department of Biochemistry and Molecular Biology, University of Bari, Via Orabona 4, 70126 Bari, Italy. m.g.liuzzi@biologia.uniba.it

Brain : a Journal of Neurology
|December 10, 2003
PubMed
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Antiretroviral drugs zidovudine (AZT) and indinavir (IDV) inhibit matrix metalloproteinases (MMPs) in glial cells. This suggests potential therapeutic uses for AZT and IDV in neurological disorders involving MMPs.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Human immunodeficiency virus (HIV) infection can lead to neurological disorders.
  • Matrix metalloproteinases (MMPs), particularly gelatinases, are implicated in these neurological conditions.
  • Glial cells are a source of MMPs involved in disease pathogenesis.

Purpose of the Study:

  • To investigate the effect of common antiretroviral drugs on MMP activity in glial cells.
  • To determine if zidovudine (AZT) and indinavir (IDV) modulate MMP-2 and MMP-9 expression in astrocytes and microglia.

Main Methods:

  • Primary rat astrocyte and microglial cultures were treated with AZT or IDV.
  • Cells were activated with lipopolysaccharide (LPS).
  • MMP-2 and MMP-9 levels were assessed using gelatin zymography, western blot, and RT-PCR.

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Main Results:

  • Astrocyte and microglial cells express MMP-2 mRNA and protein.
  • LPS increased MMP-2 in astrocytes but not microglia.
  • AZT and IDV inhibited MMP-2 in astrocytes and MMP-9 in both cell types upon LPS stimulation.
  • These drug effects were independent of antiviral activity.

Conclusions:

  • AZT and IDV directly interfere with MMP production in glial cells.
  • The findings suggest a potential therapeutic role for AZT and IDV in neurological diseases associated with MMPs.
  • This highlights a non-antiviral mechanism of action for these antiretroviral drugs.