Activation of nuclear factor kB in brains from children with HIV‐I encephalitis

S. C. Dollard, H. J. James, L. R. Sharer, L. G. Epsteint, H. A. Gelbardt, S. Dewhurst*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Human immunodeficiency virus type 1 (HIV‐1) infection of the central nervous system is associated with decreased neuronal density in discrete areas of the brain. Neuronal loss may occur via apoptosis, initiated by soluble neurotoxic factors secreted from HIV‐1 infected macrophages and microglia. To examine furlher the molecular events involved in HIV‐1 neuropathogenesis. we assessed the activity of NFkB. an inducible transcription factor involved in the activation of multiple pro‐inflammatory, and potentially neurotoxic, genes. NFkB was analysed by immunocytochemistry using specific antisera to the NFkB p. 50 and p. (75 subunits. Brains from children with HIV‐1 encephalitis and progressive encephalopathy were found to contain increased numbers of NFkB immunoreactive cells, relative to control brains (HIV‐I negative, or HIV‐1 positive nithout encephalitis). Double‐labelling studies using antibodies to CD68, or RCA‐1 lectin, markers for cells of monocyte/ macrophage lineage, revealed an increase in the number of microglia and macrophages with nuclear itnmuno‐reactivity Ior NFkB in association with HIV‐1 encephalitis. NFkB positive multinucleated giant cells were also detected, as were cells which contained both NFkB and HIV‐I antigen. In contrast, the number of neurons and GFAP‐positive astrocytes that were immunoreactive for NFkB was approximately the same in all groups of subjects. These data are consistent with the hypothesis that persistent, high‐level activation of NEkB may promote the sustained production of neurotoxins by microglia and macrophages during HIV‐1 encephalitis.

Original languageEnglish (US)
Pages (from-to)518-528
Number of pages11
JournalNeuropathology and Applied Neurobiology
Volume21
Issue number6
DOIs
StatePublished - Dec 1995

Keywords

  • acquired iminunodeficiency syndrome (AIDS)
  • human immunodeficiency virus type 1 (HIV‐1)
  • microglia
  • neuropathogenesis
  • nuclear factor kB (NFkB)
  • tnacrophage

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

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