HIV-1-infected macrophages induce astrogliosis by SDF-1alpha and matrix metalloproteinases

Biochem Biophys Res Commun. 2005 Nov 4;336(4):1214-20. doi: 10.1016/j.bbrc.2005.08.251.


Brain macrophages/microglia and astrocytes are known to be involved in the pathogenesis of HIV-1-associated dementia (HAD). To clarify their interaction and contribution to the pathogenesis, HIV-1-infected or uninfected macrophages were used as a model of brain macrophages/microglia, and their effects on human astrocytes in vitro were examined. The culture supernatants of HIV-1-infected or uninfected macrophages induced significant astrocyte proliferation, which was annihilated with a neutralizing antibody to stromal cell-derived factor (SDF)-1alpha or a matrix metalloproteinase (MMP) inhibitor. In these astrocytes, CXCR4, MMP, and tissue inhibitors of matrix metalloproteinase mRNA expression and SDF-1alpha production were significantly up-regulated. The supernatants of infected macrophages were always more effective than those of uninfected cells. Moreover, the enhanced production of SDF-1alpha was suppressed by the MMP inhibitor. These results indicate that the activated and HIV-1-infected macrophages can indirectly induce astrocyte proliferation through up-regulating SDF-1alpha and MMP production, which implies a mechanism of astrogliosis in HAD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / pathology
  • Astrocytes / physiology*
  • Astrocytes / virology
  • Brain / pathology
  • CD4 Antigens / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / metabolism*
  • HIV-1 / physiology*
  • Humans
  • Macrophage Activation
  • Macrophages / physiology*
  • Macrophages / virology
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Receptors, CCR5 / metabolism
  • Receptors, CXCR4 / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Up-Regulation


  • CD4 Antigens
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Receptors, CCR5
  • Receptors, CXCR4
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9