TNF-related apoptosis-inducing ligand mediates human neuronal apoptosis: Links to HIV-1-associated dementia

Lisa A. Ryan, Hui Peng, David A. Erichsen, Yunlong Huang, Yuri Persidsky, You Zhou, Howard E. Gendelman, Jialin Zheng

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

TNF-related apoptosis-inducing ligand (TRAIL) is a type II integral membrane protein that interacts with multiple receptors and cell types including neurons. In this report, TRAIL protein levels were increased in human monocyte-derived macrophages (MDM) after HIV-1 infection and immune activation. In HIV-1 encephalitic (HIVE) human brain tissue, TRAIL-expressing macrophages were found in association with active caspase-3 positive neurons. Cytotoxic TRAIL receptors 1 and 2 were expressed on neurons in primary human fetal cultures and HIV-1 encephalitic brain tissue. Furthermore, TRAIL induced a dose-dependent effect on neuronal apoptosis. These results support a role for TRAIL in mononuclear phagocyte (MP)-mediated neurotoxicity in HIV-1-associated dementia (HAD).

Original languageEnglish (US)
Pages (from-to)127-139
Number of pages13
JournalJournal of Neuroimmunology
Volume148
Issue number1-2
DOIs
StatePublished - Mar 2004

Keywords

  • Apoptosis
  • Caspase
  • HIV-1 encephalitis
  • Macrophage
  • Neurotoxicity
  • TRAIL

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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