Premium
Role of reactive oxygen species in LPS‐induced production of prostaglandin E 2 in microglia
Author(s) -
Wang Tongguang,
Qin Liya,
Liu Bin,
Liu Yuxin,
Wilson Belinda,
Eling Thomas E.,
Langenbach Robert,
Taniura Seijiro,
Hong JauShyong
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02242.x
Subject(s) - catalase , microglia , reactive oxygen species , nadph oxidase , superoxide dismutase , lipopolysaccharide , prostaglandin e2 , chemistry , intracellular , superoxide , western blot , prostaglandin , nitric oxide , pharmacology , biochemistry , oxidative stress , microbiology and biotechnology , inflammation , biology , enzyme , endocrinology , immunology , organic chemistry , gene
We determined the roles of reactive oxygen species (ROS) in the expression of cyclooxygenase‐2 (COX‐2) and the production of prostaglandin E 2 (PGE 2 ) 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 PGE 2 . Diphenylene iodonium (DPI), a non‐specific NADPH oxidase inhibitor, decreased LPS‐induced PGE 2 production. In addition, microglia from NADPH oxidase‐deficient mice produced less PGE 2 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 PGE 2 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 PGE 2 during the activation process of microglia. Thus, inhibiting NADPH oxidase activity and subsequent ROS generation in microglia can reduce COX‐2 expression and PGE 2 production. These findings suggest a potential therapeutic intervention strategy for the treatment of inflammation‐mediated neurodegenerative diseases.