Abstract |
Microsomal prostaglandin E2 synthase (mPGES)-1 is an inducible protein recently shown to be an important enzyme in inflammatory prostaglandin E2 ( PGE2) production in some peripheral inflammatory lesions. However, in inflammatory sites in the brain, the induction of mPGES-1 is poorly understood. In this study, we demonstrated the expression of mPGES-1 in the brain parenchyma in a lipopolysaccharide (LPS)-induced inflammation model. A local injection of LPS into the rat substantia nigra led to the induction of mPGES-1 in activated microglia. In neuron-glial mixed cultures, mPGES-1 was co-induced with cyclooxygenase-2 (COX-2) specifically in microglia, but not in astrocytes, oligodendrocytes or neurons. In microglia-enriched cultures, the induction of mPGES-1, the activity of PGES and the production of PGE2 were preceded by the induction of mPGES-1 mRNA and almost completely inhibited by the synthetic glucocorticoid dexamethasone. The induction of mPGES-1 and production of PGE2 were also either attenuated or absent in microglia treated with mPGES-1 antisense oligonucleotide or microglia from mPGES-1 knockout (KO) mice, respectively, suggesting the necessity of mPGES-1 for microglial PGE2 production. These results suggest that the activation of microglia contributes to PGE2 production through the concerted de novo synthesis of mPGES-1 and COX-2 at sites of inflammation of the brain parenchyma.
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Authors | Yuri Ikeda-Matsuo, Yuji Ikegaya, Norio Matsuki, Satoshi Uematsu, Shizuo Akira, Yasuharu Sasaki |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 94
Issue 6
Pg. 1546-58
(Sep 2005)
ISSN: 0022-3042 [Print] England |
PMID | 16000148
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Inflammation Mediators
- Lipopolysaccharides
- Oligonucleotides, Antisense
- RNA, Messenger
- Cyclooxygenase 2
- Prostaglandin-Endoperoxide Synthases
- Intramolecular Oxidoreductases
- Prostaglandin-E Synthases
- Ptges protein, mouse
- Dinoprostone
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Topics |
- Animals
- Cells, Cultured
- Coculture Techniques
- Cyclooxygenase 2
- Dinoprostone
(biosynthesis)
- Encephalitis
(chemically induced, metabolism, physiopathology)
- Enzyme Activation
(drug effects, physiology)
- Female
- Gliosis
(chemically induced, metabolism, physiopathology)
- Inflammation Mediators
(pharmacology)
- Intramolecular Oxidoreductases
(antagonists & inhibitors, genetics, metabolism)
- Lipopolysaccharides
(pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microglia
(drug effects, metabolism)
- Microsomes
(enzymology)
- Neurons
(drug effects, metabolism)
- Oligonucleotides, Antisense
(pharmacology)
- Prostaglandin-E Synthases
- Prostaglandin-Endoperoxide Synthases
(drug effects, metabolism)
- RNA, Messenger
(drug effects, metabolism)
- Rats
- Rats, Wistar
- Substantia Nigra
(drug effects, metabolism, physiopathology)
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