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Updated: Aug 17, 2026
Magnetic Isolation of Microglial Cells from Neonate Mouse for Primary Cell Cultures
Published on: July 25, 2022
Microglia-specific expression of microsomal prostaglandin E2 synthase-1 contributes to lipopolysaccharide-induced
Yuri Ikeda-Matsuo1, Yuji Ikegaya, Norio Matsuki
1Laboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan. matsuoy@pharm.kitasato-u.ac.jp
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.
Insights
Microsomal prostaglandin E2 synthase-1 (mPGES-1) is induced in activated brain microglia during inflammation. This enzyme is essential for prostaglandin E2 (PGE2) production in the brain parenchyma.
Area of Science:
- Neuroscience
- Inflammation Research
- Biochemistry
Background:
- Microsomal prostaglandin E2 synthase-1 (mPGES-1) is crucial for prostaglandin E2 (PGE2) production in peripheral inflammation.
- The role and induction of mPGES-1 in brain inflammatory sites remain poorly understood.
Purpose of the Study:
- To investigate the expression and role of mPGES-1 in the brain during inflammation.
- To elucidate the cellular sources and regulatory mechanisms of mPGES-1 in the central nervous system.
Main Methods:
- Lipopolysaccharide (LPS)-induced inflammation model in rat substantia nigra.
- Primary neuron-glial and microglia-enriched cultures.
- Analysis of mPGES-1 and cyclooxygenase-2 (COX-2) expression.
- Use of mPGES-1 antisense oligonucleotide and knockout mice.
- Measurement of PGE2 production.
Main Results:
- LPS injection induced mPGES-1 expression in activated microglia in the rat brain.
- mPGES-1 was co-induced with COX-2 specifically in microglia, not other brain cells.
- Microglial mPGES-1 induction preceded PGE2 production and was inhibited by dexamethasone.
- mPGES-1 deficiency (antisense or knockout) abolished or attenuated microglial PGE2 production.
Conclusions:
- Microglial activation drives PGE2 production in the brain parenchyma during inflammation.
- The de novo synthesis of mPGES-1 and COX-2 in microglia is critical for this process.
- mPGES-1 is a key enzyme mediating neuroinflammation via PGE2 synthesis.
