The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-alpha
Abstract
To investigate the induction of cytokines as a possible mechanism for the neurotoxicity of the HIV-1 envelope protein gp120. The gp120 protein was tested directly on primary human brain cultures to examine its ability to induce cytokines and its neurotoxicity on human neural cells because gp120 is known to be toxic to rodent ganglion cultures, and neural cells such as astrocytes and microglia produce cytokines when stimulated. Primary cultures of human brain cell aggregates, astrocytes and macrophages were exposed to HIV-1 recombinant (r) gp120SF2. Induction of cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR); neurotoxicity of rgp120SF2 and interleukin (IL)-6 on human brain cultures was examined by electron microscopy. ELISA and RT-PCR studies revealed that rgp120SF2 induced IL-6 and tumor necrosis factor (TNF)-alpha in brain cultures; IL-6 could also be induced by TNF-alpha added to brain cultures. Both IL-6 and TNF-alpha were upregulated in astrocytes and macrophage cultures on rgp120SF2 treatment. Ultrastructural studies demonstrated that IL-6 treatment for 72 h induced large cytoplasmic vacuoles in neural cells with morphology consistent with neu...Continue Reading
Citations
In vivo expression of proinflammatory cytokines in HIV encephalitis: an analysis of 11 autopsy cases
HIV-1 gp120 modulates hypothalamic cytokine mRNAs in vivo: implications to cytokine feedback systems
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