Gp-41-mediated astrocyte inducible nitric oxide synthase mRNA expression: Involvement of interleukin-1β production by microglia

Shuxian Hu, Humaira Ali, Wen Sheng, Laura C. Ehrlich, Phillip K. Peterson, Chun C. Chao

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Mechanisms underlying human immunodeficiency virus-1 encephalopathy are not completely known; however, recent studies suggest that the viral protein gp41 may be neurotoxic via activation of inducible nitric oxide synthase (iNOS) in glial cells. In the present study, we investigated the NO- generating activity of primary human fetal astrocytes in response to gp41 and the relationship to microglial cell production of interleukin-1 (IL-1). Gp41 failed to trigger iNOS mRNA expression in highly enriched (>99%) astrocyte or microglial cell cultures. However, gp41-treated microglia released a factor(s) that triggered iNOS mRNA expression and NO production in astrocytes. Because IL-1 receptor antagonist protein blocked gp41-induced NO production, a pivotal role was suggested for microglial cell IL-1 production in astrocyte iNOS expression. Also, gp41 induced IL-1β mRNA expression and IL-1 production in microglial cell but not astrocyte cultures. Using specific inhibitors, we found that gp41-induced IL-1β production in microgila was mediated via a signaling pathway involving protein-tyrosine kinase. These data support the hypothesis that gp41 induces astrocyte NO production indirectly by triggering upregulation of microglial cell IL-1 expression.

Original languageEnglish (US)
Pages (from-to)6468-6474
Number of pages7
JournalJournal of Neuroscience
Volume19
Issue number15
DOIs
StatePublished - Aug 1 1999

Keywords

  • Astrocytes
  • Cytokines
  • Human immunodeficiency virus-1
  • Interleukin- 1
  • Microgila
  • Nitric oxide
  • Nitric oxide synthase
  • Protein-tyrosine kinase

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