Cell Immunol. 1996 Aug 25;172(1):77-83. Unique Identifier : AIDSLINE
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-alpha, 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-1IIIB and HIV-1SF2, of the HIV-1
virus on the production of NO, TNF-alpha, IL-1 alpha, IL-1 beta, and
IL-6 in murine primary mixed glial cell cultures. The glial cells
exposed to HIV-1IIIB gp120 released NO, TNF-alpha, and IL-6 in a
dose-dependent manner, whereas IL-1 alpha and IL-1 beta were
undetectable. The cells exposed to HIV-1SF2 gp120 increased the release
of IL-6 only. The gp120-induced effects were significantly enhanced by
priming glial cells with IFN-gamma. To investigate the cellular sources
and mechanisms of the gp120-induced IL-6 production, in situ
hybridization with mRNA for IL-6 was performed in HIV-1IIIB gp120- or
HIV-1SF2 gp120-stimulated microgliaenriched or astrocyte-enriched
cultures. HIV-1IIIB gp120 or HIV-1SF2 gp120 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-alpha, IL-1, or IL-6 from glial cells is
differentially regulated by HIV-1IIIB gp120 and HIV-1SF2 gp120. 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.
*Cytokines/BIOSYNTHESIS *HIV Envelope Protein gp120/IMMUNOLOGY
*HIV-1/IMMUNOLOGY *Neuroglia/IMMUNOLOGY *Nitric Oxide/BIOSYNTHESIS