Document 0643
 DOCN  M95A0643
 TI    The HIV membrane gp 120 protein is toxic to human brain cell cultures
       through the induction of interleukin-6 (IL-6) and tumor necrosis
       factor-alpha(TNF-alpha). American Pediatric Society 104th annual meeting
       and Society for Pediatric Research 63rd annual meeting; 1994 May 2-5;
       Seattle.
 DT    9510
 AU    Yeung M; Pulliam L; Lau A; Dept Pediatrics, San Francisco Gen Hosp, CA,
       USA.
 SO    Pediatr AIDS HIV Infect. 1994 Oct;5(5):314 (unnumbered abstract). Unique
       Identifier : AIDSLINE AIDS/95330401
 AB    The AIDS dementia complex is a common and an important cause of
       morbidity in children with HIV infection. It is characterized by
       developmental delay, mental changes, and motor defects. We hypothesize
       that in AIDS dementia, HIV-1 gp 120 induces neurotoxicity through an
       uncontrolled induction of cytokines produced by microglia/macrophages
       and astrocytes. We investigated the induction of IL-6 and TNF-alpha by
       gp 120 in primary human astrocytes, blood macrophages as well as in our
       previously described re-aggregated human fetal brain cell model.
       Following recombinant gp 120 (0.1 or 1 nM; Chiron Corp, Emeryville, CA)
       treatment, the brain cell cultures were examined by histological and
       ultrastructural studies, and flow cytometry with antibodies against
       specific neural cell markers. Cytokine induction in these brain cultures
       was measured by reverse transcription-polymerase chain reaction for
       cytokine mRNA using specific primers and by ELISA and bioassay for
       cytokine proteins. Upon gp 120 treatment for 24h, both IL-6 and
       TNF-alpha were upregulated in these cell cultures. In addition,
       TNF-alpha induced IL-6 significantly in the brain cultures. Treatment
       with gp 120 for 7 days induced chromatin condensation along the inner
       margin of the nuclear envelope of neural cells. IL-6 also induced large
       cytoplasmic vacuoles in the neural cells after 72h of gp 120. These
       morphological changes are suggestive of apoptosis. TNF-alpha is known to
       damage myelin, induce apoptosis in oligodendrocytes, and decrease
       expression in astrocyte-specific glial fibrillary acidic protein.
       Therefore, an un-regulated gp 120-induced expression of IL-6 and
       TNF-alpha can be neurotoxic and may contribute to the neuropathology
       associated with AIDS dementia.
 DE    Apoptosis  AIDS Dementia Complex/METABOLISM
       Brain/*METABOLISM/ULTRASTRUCTURE  Cells, Cultured
       Chromatin/ULTRASTRUCTURE  Human  HIV Envelope Protein gp120/*TOXICITY
       Interleukin-6/*BIOSYNTHESIS/PHARMACOLOGY  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  Tumor Necrosis
       Factor/*BIOSYNTHESIS/PHARMACOLOGY  Vacuoles/ULTRASTRUCTURE  MEETING
       ABSTRACT  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).