title: Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra.
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.
authors: Department of Anatomy and Neurobiology, University of Kentucky, Medical Center, KY 40536, USA; Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
authors: Toyoko
authors: T
authors: Arimoto
authors: Dong-Young
authors: DY
authors: Choi
authors: Xin
authors: X
authors: Lu
authors: Mei
authors: M
authors: Liu
authors: Xuan V
authors: XV
authors: Nguyen
authors: Naiying
authors: N
authors: Zheng
authors: Charles A
authors: CA
authors: Stewart
authors: Hyoung-Chun
authors: HC
authors: Kim
authors: Guoying
authors: G
authors: Bing
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D016753:Interleukin-10 / Q000502:physiology*; D008070:Lipopolysaccharides; D008297:Male; D017628:Microglia / Q000378:metabolism; D008854:Microscopy, Electron; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D016753:Interleukin-10