TY - JOUR
T1 - The effects of the HIV-1 envelope protein gp120 on the production of nitric oxide and proinflammatory cytokines in mixed glial cell cultures
AU - Kong, Ling Yuan
AU - Wilson, Belinda C.
AU - McMillian, Michael K.
AU - Bing, Guoying
AU - Hudson, Pearlie M.
AU - Hong, Jau Shyong
PY - 1996/8/25
Y1 - 1996/8/25
N2 - 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 gp1200-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(IIIB) and HIV-(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(IIIB) gp120 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(SF2) gp120 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 situ hybridization with mRNA for IL-6 was performed in HIV-1(IIIB) gp120- or HIV-1(SF2) gp120-stimulated microglia-enriched or astrocyte-enriched cultures. HIV-1(IIIB) gp120 or HIV-1(SF2) 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-α, IL-1, or IL-6 from glial cells is differentially regulated by HIV-1(IIIB) gp120 and HIV-1(SF2) 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.
AB - 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 gp1200-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(IIIB) and HIV-(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(IIIB) gp120 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(SF2) gp120 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 situ hybridization with mRNA for IL-6 was performed in HIV-1(IIIB) gp120- or HIV-1(SF2) gp120-stimulated microglia-enriched or astrocyte-enriched cultures. HIV-1(IIIB) gp120 or HIV-1(SF2) 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-α, IL-1, or IL-6 from glial cells is differentially regulated by HIV-1(IIIB) gp120 and HIV-1(SF2) 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.
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U2 - 10.1006/cimm.1996.0217
DO - 10.1006/cimm.1996.0217
M3 - Article
C2 - 8806809
AN - SCOPUS:0030601322
SN - 0008-8749
VL - 172
SP - 77
EP - 83
JO - Cellular Immunology
JF - Cellular Immunology
IS - 1
ER -