Protective effects of an anti-inflammatory cytokine, interleukin-4, on motoneuron toxicity induced by activated microglia

Weihua Zhao, Wenjie Xie, Qin Xiao, David Beers, Stanley H. Appel

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Microglia-mediated cytotoxicity has been implicated in models of neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease, but few studies have documented how neuroprotective signals might mitigate such cytotoxicity. To explore the neuroprotective mechanism of anti-inflammatory cytokines, we applied interleukin-4 (IL-4) to primary microglial cultures activated by lipopolysaccharide as well as to activated microglia cocultured with primary motoneurons. lipopolysaccharide increased nitric oxide and superoxide (O 2 .-) and decreased insulin-like growth factor-1 (IGF-1) release from microglial cultures, and induced motoneuron injury in microglia-motoneuron cocultures. However, lipopolysaccharide had minimal effects on isolated motoneuron cultures. IL-4 interaction with microglial IL-4 receptors suppressed O2 - and nitric oxide release, and lessened lipopolysaccharide-induced microglia-mediated motoneuron injury. The extent of nitric oxide suppression correlated directly with the extent of motoneuron survival. Although IL-4 enhanced release of free IGF-1 from microglia in the absence of lipopolysaccharide, it did not enhance free IGF-1 release in the presence of lipopolysaccharide. These data suggest that IL-4 may provide a significant immunomodulatory signal which can protect against microglia-mediated neurotoxicity by suppressing the production and release of free radicals.

Original languageEnglish (US)
Pages (from-to)1176-1187
Number of pages12
JournalJournal of Neurochemistry
Volume99
Issue number4
DOIs
StatePublished - Nov 2006

Keywords

  • Insulin-like growth factor-1
  • Interleukin-4
  • Microglia
  • Motoneuron
  • Nitric oxide
  • Superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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