The Effects of the HIV-1 Envelope Protein gp120 on the Production of Nitric Oxide and Proinflammatory Cytokines in Mixed Glial Cell Cultures

doi:10.1006/cimm.1996.0217

Cellular Immunology

Volume 172, Issue 1, 25 August 1996, Pages 77-83

https://doi.org/10.1006/cimm.1996.0217 Get rights and content

Abstract

Although the neurotoxicity induced by the HIV envelope protein, gp120, has been demonstrated to require the presence of glial cells (microglia/astrocytes), the mechanisms for the gp120-induced neurotoxicity are not well understood. Moreover, the neurotoxic potencies of gp120s obtained from various HIV isolates are different. Since nitric oxide (NO) and proinflammatory cytokines (TNF-α, IL-1, IL-6) produced by glial cells have been involved in the neuropathogenesis of various diseases, this study examined the effects of gp120 obtained from two strains, HIV-1_IIIBand HIV-1_SF2, of the HIV-1 virus on the production of NO, TNF-α, IL-1α, IL-1β, and IL-6 in murine primary mixed glial cell cultures. The glial cells exposed to HIV-1_IIIBgp120 released NO, TNF-α, and IL-6 in a dose-dependent manner, whereas IL-1α and IL-1β were undetectable. The cells exposed to HIV-1_SF2gp120 increased the release of IL-6 only. The gp120-induced effects were significantly enhanced by priming glial cells with IFN-γ. To investigate the cellular sources and mechanisms of the gp120-induced IL-6 production,in situhybridization with mRNA for IL-6 was performed in HIV-1_IIIBgp120- or HIV-1_SF2gp120-stimulated microglia-enriched or astrocyte-enriched cultures. HIV-1_IIIBgp120 or HIV-1_SF2gp120 induced the expression of IL-6 mRNA in both microglia-enriched and astrocyte-enriched cultures, indicating that both microglia and astrocytes produce IL-6, and that the transcriptional regulation is involved in the gp120-induced IL-6 production. Taken together, these results demonstrate that the production of NO, TNF-α, IL-1, or IL-6 from glial cells is differentially regulated by HIV-1_IIIBgp120 and HIV-1_SF2gp120. These results may provide insights into the roles of NO and proinflammatory cytokines in the neurotoxicity of gp120s and the neuropathology of different strains of HIV-1 viruses.

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Regular ArticleThe Effects of the HIV-1 Envelope Protein gp120 on the Production of Nitric Oxide and Proinflammatory Cytokines in Mixed Glial Cell Cultures

Abstract

Regular Article
The Effects of the HIV-1 Envelope Protein gp120 on the Production of Nitric Oxide and Proinflammatory Cytokines in Mixed Glial Cell Cultures