Cytokine-mediated neuronal apoptosis

Shuxian Hu, P. K. Peterson, C. C. Chao

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

Cytokines have been reported to induce neuronal injury via the free radical nitric oxide (NO); however, the precise mechanism underlying cytokine-mediated neurotoxicity is unclear. We investigated the hypothesis that cytokine-mediated neurotoxicity in primary cultures of human fetal neurons occurs via an apoptotic mechanism triggered by NO. Treatment of mixed neuronal/glial cell cultures with interferon (IFN)-γ plus interleukin (IL)-1β for 13 days induced a high output of NO accompanied by marked neuronal loss. The NO synthase inhibitor N-monomethyl-L-arginine (NMMA) significantly attenuated cytokine-induced neuronal loss, confirming the involvement of NO. Cytokine-mediated neuronal injury was accompanied by morphologic changes and a DNA fragmentation pattern consistent with apoptosis. Treatment of neuronal cell cultures with NMMA protected against cytokine-mediated apoptotic death. These findings, using primary human neuronal cell cultures, support the hypothesis that cytokine-mediated neurotoxicity involving NO proceeds via an apoptotic mechanism. These findings could lead to the development of new therapies for neurodegenerative diseases involving glia, cytokines, and NO.

Original languageEnglish (US)
Pages (from-to)427-431
Number of pages5
JournalNeurochemistry International
Volume30
Issue number4-5
DOIs
StatePublished - Apr 1997

Bibliographical note

Funding Information:
This study was supported in part by USPHS grants DA-04381, DA-09924 and a grant from the Alzheimer's Association.

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