α-Synuclein potentiates interleukin-1β-induced CXCL10 expression in human A172 astrocytoma cells

NEUROSCIENCE LETTERS

卷:507

Article

Tousi, Neda Saffarian¹  Buck, Daniel J.¹  Curtis, J. Thomas¹  Davis, Randall L.¹ 

[1] Oklahoma State Univ, Ctr Hlth Sci, Dept Pharmacol Physiol, Tulsa, OK 74107 USA

关键词: Parkinson's disease;    alpha-Synuclein;    Astrocyte;    Neuroinflammation;    Chemokine;    NF-kappa B;   

DOI  :  10.1016/j.neulet.2011.12.001

来源: Elsevier

【 摘 要 】

Neuroinflammation and neuronal degeneration observed in Parkinson's disease (PD) has been attributed in part to glial-mediated events. Increased expression of proinflammatory cytokines and abnormal accumulation of the neuronal protein, alpha-synuclein in the brain are also characteristic of PD. While increasing evidence suggests that astrocytes contribute to neuroinflammation and dopaminergic neuronal degeneration associated with PD, there remains much to learn about these astroglial-mediated events. Therefore, we investigated the in vitro effects of interleukin-1 beta (IL-1 beta) and alpha-synuclein on astroglial expression of interferon-gamma inducible protein-10 (CXCL10), a proiriflammatory and neurotoxic chemokine. IL-1 beta-induced CXCL10 protein expression was potentiated by co-exposure to alpha-synuclein. alpha-Synuclein did not significantly affect IL-1 beta-induced CXCL10 mRNA expression, but did mediate increased CXCL10 mRNA stability, which may explain, in part, the increased levels of secreted CXCL10 protein. Future investigations are warranted to more fully define the mechanism by which alpha-synuclein enhances IL-1 beta-induced astroglial CXCL10 expression. These findings highlight the importance of alpha-synuclein in modulating inflammatory events in astroglia. These events may be particularly relevant to the pathology of CNS disorders involving alpha-synuclein accumulation, including PD and HIV-1 associated dementia. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free