Role of microglia in inflammation-mediated degeneration of dopaminergic neurons: neuroprotective effect of interleukin 10.
Inflammation in the brain has been recognized to play an increasingly important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Inflammation-mediated neurodegeneration involves activation of the brain's resident immune cells, the microglia, which produce proinflammatory and neurotoxic factors including cytokines, reactive oxygen species (ROS), nitric oxide, and eicosanoids that directly or indirectly cause neurodegeneration. In this study, we report that IL-10, an immunosuppressive cytokine, reduced the inflammation-mediated degeneration of dopaminergic (DA) neurons through the inhibition of microglial activation. Pretreatment of rat mesencephalic neuronglia cultures with IL-10 significantly attenuated the lipopolysaccharide (LPS) induced DA neuronal degeneration. The neuroprotective effect of IL-10 was attributed to inhibition of LPS-stimulated microglial activation. IL-10 significantly inhibited the microglial production of tumor necrosis factor alpha (TNF-alpha), nitric oxide, ROS and superoxide free radicals after LPS stimulation.
Qian
L
L
Comprehensive Center for Inflammatory Disorders, University of North Carolina, Chapel Hill, NC 27599-7455, USA.
Hong
J S
JS
Flood
P M
PM
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D007202:Indicators and Reagents; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D009573:Nitrites; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016753:Interleukin-10; D004298:Dopamine