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Article: The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-α

TitleThe HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-α
Authors
Issue Date1995
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.AIDSonline.com
Citation
Aids, 1995, v. 9 n. 2, p. 137-143 How to Cite?
AbstractObjective: To investigate the induction of cytokines as a possible mechanism for the neurotoxicity of the HIV-1 envelope protein gp120. Design: 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. Methods: Primary cultures of human brain cell aggregates, astrocytes and macrophages were exposed to HIV-1 recombinant(r) gp120(SF2) Induction of cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR); neurotoxicity of rgp120(SF2) and interleukin (IL)-6 on human brain cultures was examined by electron microscopy. Results: ELISA and RT-PCR studies revealed that rgp120(SF2) induced IL-6 and tumor necrosis factor (TNF)-α in brain cultures; IL-6 could also be induced by TNF-α added to brain cultures. Both IL-6 and TNF-α were upregulated in astrocytes and macrophage cultures on rgp120(SF2) treatment. Ultrastructural studies demonstrated that IL-6 treatment for 72h induced large cytoplasmic vacuoles in neural cells with morphology consistent with neurons; rgp120(SF2) treatment for 7 days resulted in chromatin condensation along the inner margins of nuclear envelopes of neural cells. Conclusions: Our results demonstrated that HIV-1 rgp120(SF2) can upregulate at least two known neurotoxic cytokines, IL-6 and TNF-α, which may injure neural cells and contribute to the neuropathology observed in AIDS dementia patients.
Persistent Identifierhttp://hdl.handle.net/10722/170277
ISSN
2015 Impact Factor: 4.407
2015 SCImago Journal Rankings: 3.112
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYeung, MCen_US
dc.contributor.authorPulliam, Len_US
dc.contributor.authorLau, ASen_US
dc.date.accessioned2012-10-30T06:07:10Z-
dc.date.available2012-10-30T06:07:10Z-
dc.date.issued1995en_US
dc.identifier.citationAids, 1995, v. 9 n. 2, p. 137-143en_US
dc.identifier.issn0269-9370en_US
dc.identifier.urihttp://hdl.handle.net/10722/170277-
dc.description.abstractObjective: To investigate the induction of cytokines as a possible mechanism for the neurotoxicity of the HIV-1 envelope protein gp120. Design: 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. Methods: Primary cultures of human brain cell aggregates, astrocytes and macrophages were exposed to HIV-1 recombinant(r) gp120(SF2) Induction of cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR); neurotoxicity of rgp120(SF2) and interleukin (IL)-6 on human brain cultures was examined by electron microscopy. Results: ELISA and RT-PCR studies revealed that rgp120(SF2) induced IL-6 and tumor necrosis factor (TNF)-α in brain cultures; IL-6 could also be induced by TNF-α added to brain cultures. Both IL-6 and TNF-α were upregulated in astrocytes and macrophage cultures on rgp120(SF2) treatment. Ultrastructural studies demonstrated that IL-6 treatment for 72h induced large cytoplasmic vacuoles in neural cells with morphology consistent with neurons; rgp120(SF2) treatment for 7 days resulted in chromatin condensation along the inner margins of nuclear envelopes of neural cells. Conclusions: Our results demonstrated that HIV-1 rgp120(SF2) can upregulate at least two known neurotoxic cytokines, IL-6 and TNF-α, which may injure neural cells and contribute to the neuropathology observed in AIDS dementia patients.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.AIDSonline.comen_US
dc.relation.ispartofAIDSen_US
dc.subject.meshAstrocytes - Drug Effects - Metabolism - Ultrastructureen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBrain - Drug Effects - Metabolism - Ultrastructureen_US
dc.subject.meshCell Deathen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCulture Mediaen_US
dc.subject.meshDna, Complementaryen_US
dc.subject.meshHiv Envelope Protein Gp120 - Toxicityen_US
dc.subject.meshHumansen_US
dc.subject.meshInterleukin-6 - Biosynthesis - Toxicityen_US
dc.subject.meshMacrophages - Drug Effects - Ultrastructureen_US
dc.subject.meshMicroscopy, Electronen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshRna - Biosynthesisen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Biosynthesis - Toxicityen_US
dc.titleThe HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-αen_US
dc.typeArticleen_US
dc.identifier.emailLau, AS:asylau@hku.hken_US
dc.identifier.authorityLau, AS=rp00474en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid7536422-
dc.identifier.scopuseid_2-s2.0-0028853061en_US
dc.identifier.volume9en_US
dc.identifier.issue2en_US
dc.identifier.spage137en_US
dc.identifier.epage143en_US
dc.identifier.isiWOS:A1995QE48000004-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYeung, MC=7101861664en_US
dc.identifier.scopusauthoridPulliam, L=7004817966en_US
dc.identifier.scopusauthoridLau, AS=7202626202en_US

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