Journal
PARKINSONISM & RELATED DISORDERS
Volume 13, Issue -, Pages S316-S320Publisher
ELSEVIER SCI LTD
DOI: 10.1016/S1353-8020(08)70023-3
Keywords
femtomolar DPI; LPS; inflammation; microglia; ROS
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Funding
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [P60DE013079] Funding Source: NIH RePORTER
- Intramural NIH HHS Funding Source: Medline
- NIDCR NIH HHS [DE-13079] Funding Source: Medline
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In this paper we report that diphenyliodonium (DPI), a NADPH oxidase inhibitor, shows potent anti-inflammatory and neuroprotective effects at femtomolar concentrations (10(-13) to 10(-14) M) in primary midbrain cultures. Mechanistic studies revealed that DPI-elicited effects were mediated by the inhibition of LPS-induced microglial ROS production and the subsequent release of pro-inflammatory cytokine TNF alpha, and the production of nitric oxide. Further studies showed that 10(-14) M DPI significantly reduced LPS-induced ERK phosphorylation. Taken together, our results demonstrate that femtomolar concentrations of DPI exert potent anti-inflammatory and neuroprotective effects by inhibiting microglial activation through the inhibition of ERK-regulated PHOX activity. (C) 2007 Elsevier B.V. All rights reserved.
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