Regulatory Functions of Prostaglandin E2 Synthases

  • Ichiro Kudo
  • Makoto Murakami
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 525)


Prostaglandin (PG) E2, the most common prostanoid with a variety of bioactivities, has been implicated in various pathophysiologies. PGE2 is produced via three sequential enzymatic reactions: release of arachidonic acid (AA) from membrane glycerophospholipids by phospholipase A2 (PLA2), conversion of AA to PGH2 by cyclooxygenase (COX), and isomerization of PGH2 to PGE2 by PGE synthase (PGES). During last few years, multiple PGES enzymes have been identified molecularly. In this report, we will overview the structures, enzymatic properties, expression, cellular functions, and possible in vivo functions of two of these enzymes, membrane-bound PGES (mPGES)-l and cytosolic PGES (cPGES).


Arachidonic Acid Granulosa Cell Layer Rheumatoid Synovial Cell Transitional Epithelial Cell Cytosolic GSTs 
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  1. 1.
    Jakobsson PJ, et al. Identification of human PGES: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci USA 1999; 96: 7220–7225.PubMedCrossRefGoogle Scholar
  2. 2.
    Murakami M, et al. Regulation of PGE2 biosynthesis by inducible membrane-associated PGES that acts in concert with COX-2. J Biol Chem 2000; 275: 32783–32792.PubMedCrossRefGoogle Scholar
  3. 3.
    Mancini JA, et al. Cloning, expression, and up-regulation of inducible rat PGES during lipopolysaccharide-induced pyresis and adjuvant-induced arthritis. J Biol Chem 2001; 276: 4469–4475.PubMedCrossRefGoogle Scholar
  4. 4.
    Uematsu S, et al. Lipopolysaccharide-dependent PGE2 production is regulated by the glutathione-dependent PGES gene induced by the Toll-like receptor 4/MyD88/NF-IL6 pathway. J Immunol 2002; 168: 5811–5816.PubMedGoogle Scholar
  5. 5.
    Naraba H, et al. Transcriptional regulation of the mPGES gene: essential role of the transcription factor Egr-1. J Biol Chem 2002; 277: 28601–28608.PubMedCrossRefGoogle Scholar
  6. 6.
    Stichtenoth DO, et al. mPGES is regulated by proinflammatory cytokines and glucocorticoids in primary rheumatoid synovial cells. J Immunol 2001; 167: 469–474.PubMedGoogle Scholar
  7. 7.
    Yamagata K, et al. Coexpression of mPGES with COX-2 in brain endothelial cells of rats during endotoxin-induced fever. J Neurosci 2001; 21: 2669–2677.PubMedGoogle Scholar
  8. 8.
    Yoshimatsu K, et al. Inducible PGES is overexpressed in non-small cell lung cancer. Clin. Cancer Res 2001; 7: 2669–2674.PubMedGoogle Scholar
  9. 9.
    Satoh K, et al. Expression of PGES mRNA is induced in D-amyloid treated rat astrocytes. Neurosci Lett 2000; 283: 221–223.PubMedCrossRefGoogle Scholar
  10. 10.
    Filion F, et al. Molecular cloning and induction of bovine PGES by gonadotropinsin ovarian follicles prior to ovulation in vivo. J Biol Chem 2001; 276: 34323–34330.PubMedCrossRefGoogle Scholar
  11. 11.
    Lazarus M, et al. Immunohistochemical localization of mPGES-1 and COXs in male mouse reproductive organs. Endocrinology 2002; 143: 2410–2419.PubMedCrossRefGoogle Scholar
  12. 12.
    Guan Y, et al. Urogenital distribution of a mouse mPGES. Am J Phisiol Renal Physiol 2001; 281: F1173–1177.Google Scholar
  13. 13.
    Tanioka T, et al. Molecular identification of cPGES that is functionally coupled with COX-1 in immediate PGE2 biosynthesis. J Biol Chem 2000; 275:32775–21782.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Ichiro Kudo
    • 1
  • Makoto Murakami
    • 1
  1. 1.Showa UniversityShinagawa-kuJapan

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