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 journalArticlepeer-review

54 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
Pages (from-to)127-139
Number of pages13
JournalJournal of Neuroimmunology
Volume148
Issue number1-2
DOIs
StatePublished - Mar 2004

Bibliographical note

Funding Information:
This work was supported in part by research grants by the National Institutes of Health: R01 NS 41858-01 (JZ), P20 RR15635-01 (JZ and HEG) and P01 NS043985-01 (HEG and JZ). We kindly acknowledge Dr. Anuja Ghorpade for scientific support and fruitful discussion. Li Wu, David Heilman, Jiaxing Zhao, Alicia Lopez, Clancy McNally and Abby Cheloha provided technical support for this work. Ms. Shelley Herek, Mr. Nathan Erdmann, Dr. Kim Carlson and Dr. Jenae Limoges provided valuable comments and suggestions about the manuscript. Dr. Charles Kuszynski and Linda Wilkie performed the FACS analyses. Julie Ditter and Myhanh Che provided outstanding administrative support. Ms. Robin Taylor's contribution for providing outstanding support in assembling the work for publication is appreciated.

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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