| Title | Role of reactive oxygen species in LPS-induced production of prostaglandin E2 in microglia. | | Author(s) | Wang T, Qin L, Liu B, Liu Y, Wilson B, Eling TE, Langenbach R, Taniura S, Hong JS | | Institution | Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina 27709, USA. | | Source | J Neurochem 2004 Feb; 88(4):939-47. | | MeSH | Animals
Animals, Newborn
Blotting, Western
Brain
Catalase
Catecholamines
Cell Count
Cells, Cultured
Comparative Study
Cyclooxygenase 2
Dinoprostone
Dose-Response Relationship, Drug
Drug Interactions
Extracellular Space
Female
Fluoresceins
Imidazolines
Intracellular Space
Isoenzymes
Lipopolysaccharides
Mice
Mice, Inbred C57BL
Mice, Knockout
Microglia
NADPH Oxidase
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Organometallic Compounds
Pregnancy
Prostaglandin-Endoperoxide Synthases
RNA, Messenger
Rats
Rats, Inbred F344
Reactive Oxygen Species
Reverse Transcriptase Polymerase Chain Reaction
Salicylates
Superoxide Dismutase
Tetrazolium Salts
Thiazoles
| | Abstract | We determined the roles of reactive oxygen species (ROS) in the expression of cyclooxygenase-2 (COX-2) and the production of prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated microglia. LPS treatment increased intracellular ROS in rat microglia dose-dependently. Pre-treatment with superoxide dismutase (SOD)/catalase, or SOD/catalase mimetics that can scavenge intracellular ROS, significantly attenuated LPS-induced release in PGE2. Diphenylene iodonium (DPI), a non-specific NADPH oxidase inhibitor, decreased LPS-induced PGE2 production. In addition, microglia from NADPH oxidase-deficient mice produced less PGE2 than those from wild-type mice following LPS treatment. Furthermore, LPS-stimulated expression of COX-2 (determined by RT-PCR analysis of COX-2 mRNA and western blot for its protein) was significantly reduced by pre-treatment with SOD/catalase or SOD/catalase mimetics. SOD/catalase mimetics were more potent than SOD/catalase in reducing COX-2 expression and PGE2 production. As a comparison, scavenging ROS had no effect on LPS-induced nitric oxide production in microglia. These results suggest that ROS play a regulatory role in the expression of COX-2 and the subsequent production of PGE2 during the activation process of microglia. Thus, inhibiting NADPH oxidase activity and subsequent ROS generation in microglia can reduce COX-2 expression and PGE2 production. These findings suggest a potential therapeutic intervention strategy for the treatment of inflammation-mediated neurodegenerative diseases. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 14756815 |
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