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Microglia-specific expression of microsomal prostaglandin E2 synthase-1 contributes to lipopolysaccharide-induced prostaglandin E2 production.
J Neurochem. 2005 Sep; 94(6):1546-58.JN

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.

Authors+Show Affiliations

Laboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan. matsuoy@pharm.kitasato-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16000148

Citation

Ikeda-Matsuo, Yuri, et al. "Microglia-specific Expression of Microsomal Prostaglandin E2 Synthase-1 Contributes to Lipopolysaccharide-induced Prostaglandin E2 Production." Journal of Neurochemistry, vol. 94, no. 6, 2005, pp. 1546-58.
Ikeda-Matsuo Y, Ikegaya Y, Matsuki N, et al. Microglia-specific expression of microsomal prostaglandin E2 synthase-1 contributes to lipopolysaccharide-induced prostaglandin E2 production. J Neurochem. 2005;94(6):1546-58.
Ikeda-Matsuo, Y., Ikegaya, Y., Matsuki, N., Uematsu, S., Akira, S., & Sasaki, Y. (2005). Microglia-specific expression of microsomal prostaglandin E2 synthase-1 contributes to lipopolysaccharide-induced prostaglandin E2 production. Journal of Neurochemistry, 94(6), 1546-58.
Ikeda-Matsuo Y, et al. Microglia-specific Expression of Microsomal Prostaglandin E2 Synthase-1 Contributes to Lipopolysaccharide-induced Prostaglandin E2 Production. J Neurochem. 2005;94(6):1546-58. PubMed PMID: 16000148.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microglia-specific expression of microsomal prostaglandin E2 synthase-1 contributes to lipopolysaccharide-induced prostaglandin E2 production. AU - Ikeda-Matsuo,Yuri, AU - Ikegaya,Yuji, AU - Matsuki,Norio, AU - Uematsu,Satoshi, AU - Akira,Shizuo, AU - Sasaki,Yasuharu, Y1 - 2005/07/05/ PY - 2005/7/8/pubmed PY - 2005/10/28/medline PY - 2005/7/8/entrez SP - 1546 EP - 58 JF - Journal of neurochemistry JO - J. Neurochem. VL - 94 IS - 6 N2 - 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. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/16000148/Microglia_specific_expression_of_microsomal_prostaglandin_E2_synthase_1_contributes_to_lipopolysaccharide_induced_prostaglandin_E2_production_ L2 - https://doi.org/10.1111/j.1471-4159.2005.03302.x DB - PRIME DP - Unbound Medicine ER -