Skip to main content
SpringerLink
Log in

Function and Regulation of Prostaglandin Synthase 2

  • Chapter
Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 469))

Abstract

The prostanoids (prostaglandins, prostacyclins, thromboxanes) are one subset of arachidonic-acid derived lipid mediators of inflammation. The leukotrienes constitute the second major class of arachidonic-acid derived lipid mediators. A variety of inflammatory signals (including exogenous mediators such as endotoxin/lipopoly-saccharide and endogenous mediators such as inflammatory cytokines) stimulate cellular phospholipase activities. As a result, arachidonic acid is released from phospholipid membrane stores. This free arachidonic acid is converted either (i) to leukotrienes via the lipoxygenase pathway(s), or (ii) to prostanoids. The key enzyme in prostanoid biosynthesis is prostaglandin synthase (PGS), also known as cyclooxygenase (COX). PGS/COX converts free arachidonate first to prostaglandin G2 (PGG2) by a cyclooxygenase reaction, and then -in a second enzymatic step- to prostaglandin H2 (PGH2) by a hydroperoxidase reaction. PGH2 is then converted to the various prostaglandins (PGE2, PGD2, PGF2a, etc), prostacyclin, (PGI2) or thromboxane by cell-type restricted synthetases that use PGH2 as substrate. The various prostanoids have a wide range of positive and negative immuno-modulatory effects on lymphoid, myeloid, and endothelial cells. New pharmacologic agents that modulate the activity of enzymes involved in prostanoid synthesis or the expression of the genes encoding these enzymes will provide improved directions in the management of acute and chronic inflammatory diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Herschman, H.R. Primary response genes induced by growth factors and tumor promoters, In Annual Review of Biochemistry, vol. 60 (Richardson, C.C., Abelson, J.N., Meister, A., and Walsh, C.T., eds.) Annual Reviews, Inc., Palo Alto, California, pp. 281–319 (1991).

    Google Scholar 

  2. Herschman, H.R., Kujubu, D.A., Fletcher, B.S., Ma, Q-F., Varnum, B.C., Gilbert, R.S., and Reddy, S.T. “The TIS genes, primary response genes induced by growth factors and tumor promoters.” in Progress in Nucleic Acids Research and Molecular Biology, vol. 47 (Cohen, W., and Moldave, K., eds.) Academic Press, Orlando, Florida, pp. 113–148 (1994).

    Google Scholar 

  3. Kujubu, D.A., Fletcher, B.S., Varnum, B.C., Lim, R.W., and Herschman, H.R. TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J. Biol. Chem.266:12866–12872 (1991).

    PubMed  CAS  Google Scholar 

  4. Fletcher, B.S., Kujubu, D.A., Perrin, D.M., and Herschman, H.R. Structure of the Mitogen-Inducible TIS10 gene and demonstration that the TIS10 encoded protein is a functional prostaglandin G/H synthase. J. Biol. Chem.267:4338–4344 (1992).

    PubMed  CAS  Google Scholar 

  5. Xie, W., Chipman, J.G., Robertson, D.L., Erikson, R.L., and Simmons, D.L. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc. Natl Acad. Sci.88:2692–2696 (1991).

    Article  PubMed  CAS  Google Scholar 

  6. O’Banion, M.K., Sadowski, H.B., Winn, V., and Young, D.A. A serum-and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. J. Biol Chem.266: 23261–23267 (1991).

    PubMed  Google Scholar 

  7. Ryseck, R.P., Raynoschek, G, Macdonald-Bravo, H., Dorfman, K., Mattei, M., and Bravo, R. Identification of an immediate early gene, phs-B, whose protein product has prostaglandin synthase/cyclooxygenase activity. Cell Growth Differ.3:443–450 (1992).

    PubMed  CAS  Google Scholar 

  8. Hla, T., and Neilson, K. Human cyclooxygenase-2 cDNA. Proc. Natl. Acad. Sci.89:7384–7385 (1992).

    Article  PubMed  CAS  Google Scholar 

  9. Jones, D.A., Carlton, D.P., Mclntyre, T.M., Zimmerman, G.A., and Prescott, S.M. Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J. Biol. Chem.268:9049–9054 (1993).

    PubMed  CAS  Google Scholar 

  10. DuBois, R.N., Tsujii, M., Bishop, P., Awad, J.A., Makita, K., and Lanahan, A. Cloning and characterization of a growth factor-inducible cyclooxygenase gene from rat intestinal epithelial cells. Am. J. Physiol 266:G822–G827 (1994).

    PubMed  CAS  Google Scholar 

  11. Herschman, H.R., Xie, W., and Reddy, S. Inflammation, reproduction, cancer, and all that…. The regulation and role of the inducible prostaglandin synthase. BioEssays17:1031–1037 (1995).

    Article  PubMed  CAS  Google Scholar 

  12. Herschman, H.R. Prostaglandin synthase 2. Biochim. Biophys.Acta1299:125–140 (1996).

    Article  PubMed  Google Scholar 

  13. Vane, J. Towards a better aspirin. Nature 367:215–216 (1994).

    Article  PubMed  CAS  Google Scholar 

  14. Kujubu, D.A., and Herschman, H.R. Dexamethasone inhibits mitogen iduction of the TIS10 prostaglandin synthase/cyclooxygenase gene. J. Biol Chem.267:7991–7994 (1992).

    PubMed  CAS  Google Scholar 

  15. Reddy, S.T., and Herschman, H.R. Ligand-induced prostaglandin synthesis requires expression of the TIS10/PGS-2 prostaglandin synthase gene in murine fibroblasts and macrophages. J. Biol Chem.269:15473–15480 (1994).

    PubMed  CAS  Google Scholar 

  16. Morita, I., Schindler, M., Regier, M.K., Otto, J.C., Hori, T., DeWitt, D.L., and Smith, W.L. Different intracellular locations for prostaglandin endoperoxide H synthases-1 and-2. J. Biol. Chem.270:10902–10908 (1995).

    Article  PubMed  CAS  Google Scholar 

  17. Xie, W., and Herschman, H.R. v-src induces prostaglandin synthase 2 gene expression by activation of the c-Jun N-terminal kinase and the c-Jun transcription factor. J. Biol. Chem.270:27622–27628 (1995).

    Article  PubMed  CAS  Google Scholar 

  18. Xie, W., and Herschman, H.R. Transcriptional regulation of prostaglandin synthase 2 gene expression by platelet derived growth factor and serum. J. Biol Chem.271:31742–31748 (1996).

    Article  PubMed  CAS  Google Scholar 

  19. Inoue, H., Yokoyama, C, Hara, S., Tone, Y., and Tanabe, T. Transcriptional regulation of man prostaglandin-endoperoxide synthase-2 gene by lipopolysaccharide and phorbol ester in vascular endothelial cells. Involvement of both nuclear factor for interleukin-6 expression site and cAMP response element. J. Biol. Chem.270: 24965–24971 (1995).

    Article  PubMed  CAS  Google Scholar 

  20. Yamamoto, K., Arakawa, T., Ueda, N., and Yamamoto, S. Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-El cells. J. Biol. Chem.270:31315–31320 (1995).

    Article  PubMed  CAS  Google Scholar 

  21. Kawata, R., Reddy, S.T., Wolner, B., and Herschman, H.R. Prostaglandin synthase 1 and prostaglandin synthase 2 both participate in activation-induced PGD2 production in mast cells. J. Immunol.155:818–825 (1995).

    PubMed  CAS  Google Scholar 

  22. Murakami, M., Bingham, C.O. 3rd, Matsumoto, R., Austen, K.F., and Arm, J.P. IgE-dependent activation of cytokine-primed mouse cultured mast cells induces a delayed phase of prostaglandin D2 generation via prostaglandin endoperoxide synthase-2. J. Immunol.155:4445–4453 (1995).

    PubMed  CAS  Google Scholar 

  23. Reddy, S.T., and Herschman, H.R. Prostaglandin synthase-1 and prostaglandin synthase-2 are coupled to distinct phospholipases for the generation of prostaglandin D2 in activated mast cells. J. Biol Chem.72:3231–3237 (1997)

    Google Scholar 

  24. Bingham, C.O. 3rd, Murakami, M., Fujishima, H., Hunt, J.E., Austen, K.F., and Arm, J. A heparin-sensitive phospholipase A2 and prostaglandin endoperoxide synthase-2 are functionally linked in the delayed phase of prostaglandin D2 generation in mouse bone marrow-derived mast cells. J. Biol. Chem.271:25936–25944 (1996).

    Article  PubMed  CAS  Google Scholar 

  25. Fonteh, A.N., Bass, D.A., Marshall, L.A., Seeds, M., Samet, J.M., and Chilton, F.H. Evidence that secretory phospholipase A2 plays a role in arachidonic acid release and eicosanoid biosynthesis by mast cells. J. Immunol.152:5438–5446 (1994).

    PubMed  CAS  Google Scholar 

  26. Reddy, S.T, Winstead, M.V., Tischfield, J.A., and Herschman, H.R. Analysis of the secretory phospholipase A2 that mediates prostaglandin production in mast cells. J. Biol. Chem.272:13591–13596 (1997).

    Article  PubMed  CAS  Google Scholar 

  27. Reddy, S.T., and Herschman, H.R. Transcellular prostaglandin production following mast cell activation is mediated by proximal secretory phospholipase A2 and distal prostaglandin synthase 1. J. Biol. Chem.271:186–191 (1996).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Biological Chemistry and Molecular and Medical Pharmacology, UCLA School of Medicine Molecular Biology Institute, 611 Circle Drive East, Los Angeles, CA, 90025-1570, USA

    Harvey R. Herschman, Weilin Xie & Srinivasta Reddy

Authors
  1. Harvey R. Herschman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weilin Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Srinivasta Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth V. Honn

  2. Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Lawrence J. Marnett

  3. Free University Berlin, Berlin, Germany

    Santosh Nigam

  4. University of California at San Diego, San Diego, California, USA

    Edward A. Dennis

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Herschman, H.R., Xie, W., Reddy, S. (1999). Function and Regulation of Prostaglandin Synthase 2. In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E.A. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4. Advances in Experimental Medicine and Biology, vol 469. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4793-8_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4793-8_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7171-7

  • Online ISBN: 978-1-4615-4793-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation