Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra

Toyoko Arimoto, Dong Young Choi, Xin Lu, Mei Liu, Xuan V. Nguyen, Naiying Zheng, Charles A. Stewart, Hyoung Chun Kim, Guoying Bing

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Inflammation has been increasingly recognized to play an important role in the pathogenesis of Parkinson's disease (PD). Using immunocytochemistry and electron microscopy, we found that intranigral injection of lipopolysaccharide (LPS) caused marked microglial activation and a dose-dependent selective loss of dopaminergic neurons, which was mediated by apoptosis as evidenced by prominent TUNEL labeling. RNase protection assays revealed that mRNA for Bax, Fas and the pro-inflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6 and tumor necrosis factor (TNF)-α were significant increased ipsilaterally in LPS-injected side of SN, while expression of the anti-apoptotic gene Bcl-2 was decreased. Osmotic pump infusion of IL-10, a global inhibitor of cytokine synthesis, protected against LPS-induced cell death of dopaminergic neurons, with a corresponding decrease in the number of activated microglia, suggesting that the reduction in microglia-mediated release of inflammatory mediators may contribute to the anti-inflammatory effect of IL-10. Our results provide evidence that LPS induces apoptotic cell death in SNpc, which is likely through the expression of Fas, Bax, caspase-3, and the pro-inflammatory cytokines.

Original languageEnglish
Pages (from-to)894-906
Number of pages13
JournalNeurobiology of Aging
Volume28
Issue number6
DOIs
StatePublished - Jun 2007

Bibliographical note

Funding Information:
This work was supported by grants (to G.Y.B.) from NIH (NS39345) and grant from the Brain Research Center from the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea.

Keywords

  • Apoptosis
  • Dopaminergic neuron
  • Inflammation
  • Interleukin-10 (IL-10)
  • Lipopolysaccharide (LPS)
  • Microglia
  • Neurodegeneration
  • Parkinson's disease (PD)

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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