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

Abstract

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.

• Authors: Mika Okamoto, Xin Wang, Masanori Baba
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 336 Issue 4 Pg. 1214-20 (Nov 04 2005) ISSN: 0006-291X [Print] United States
• PMID: 16169519 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• AIDS Dementia Complex (pathology)
• Astrocytes (physiology, virology)
• Brain (pathology)
• CD4 Antigens (metabolism)
• Cell Proliferation
• Cells, Cultured
• Chemokine CXCL12
• Chemokines, CXC (metabolism)
• HIV-1 (physiology)
• Humans
• Macrophage Activation
• Macrophages (physiology, 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