Skip to main content
SpringerLink
Log in

Enzymatic regulation of the prostaglandin response in a human model of inflammation

  • Chapter
New Targets in Inflammation

Abstract

Prostaglandins (PG) are potent biological mediators of thrombosis and the inflammatory response1,2. Prostaglandin endoperoxide H synthase, also referred to as cyclooxygenase (COX), is a bisfunctional protein, which catalyses the first committed step in the formation of PG and thromboxanes by the sequential cyclooxygenation and peroxidation of arachidonic acid (AA) to PGH2 3,4. PGH2 is then converted to specific PGs by distinct cell specific synthases or isomerases. Mammalian cells contain two isoforms of this enzyme, COX-1 and COX-2, which are encoded by separate genes, but they are structurally homologous and have similar kinetic properties5–7.

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 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
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. FitzGerald GA. Prostaglandins and related compounds. In: Wyngaarden JB, Smith LH, Bennett JC, eds. Cecil Loeb Textbook of Medicine, 20th edn. Philadelphia: Saunders, 1995:1187–93.

    Google Scholar 

  2. Smith WL. The eicosanoids and their biochemical mechanisms of action. Biochem J. 1989;259: 315–24.

    PubMed  CAS  Google Scholar 

  3. Smith WL, Marnett U. Prostaglandin endoperoxide synthase: Structure and catalysis. Biochem Biophys Acta. 1990;1083:1–17.

    Google Scholar 

  4. Smith WL. Prostanoid biosynthesis and mechanisms of action. Am J Physiol. 1992;263: F181–91.

    PubMed  CAS  Google Scholar 

  5. Hla T, Neilson K. Human cyclooxygenase 2 cDNA. Proc Nat! Acad Sci USA. 1992;89:7384–8.

    Article  PubMed  CAS  Google Scholar 

  6. O’Bannion MK, Winn VD, Young DA. cDNA Cloning and functional activity of a glucocorticoidregulated inflammatory cyclooxygenase. Proc Nat! Acad Sci USA. 1992;89:4888–92.

    Article  Google Scholar 

  7. Hsi LC, Hoganson CW, Babcock GT, Smith WL. Characterization of a tyrosyl radical in prostaglandin endoperoxide synthase-2. Biochem Biophys Res Commun. 1994;202:1592–8.

    Article  PubMed  CAS  Google Scholar 

  8. Yamagata K, Andreasson K, Kaufmann W, Barnes CA, Worley PE Expression of a mitogen inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron. 1993;11:371–86.

    Article  PubMed  CAS  Google Scholar 

  9. O’Neill GP, Ford-Hutchinson AW. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett. 1993;330:156–60.

    PubMed  Google Scholar 

  10. Fu JY, Masferrer JL, Seibert K, Raz A, Needleman P. The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem. 1990;265:16737–40.

    PubMed  CAS  Google Scholar 

  11. Masferrer JL, Zweifel BS, Seibert K, Needleman P. Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest. 1990;86:1375–9.

    Article  PubMed  CAS  Google Scholar 

  12. Crofford LJ, Wilder RL, Ristimaki AP, Sano H, Remmers EF, Epps HR, Hla T. CyclooxygenaseI and -2 expression in rheumatoid synovial tissues. J Clin Invest. 1994;93:1095–101.

    Article  PubMed  CAS  Google Scholar 

  13. Masferrer JL, Srinivasa TR, Zweifel BS, Seibert K, Needleman P, Gilbert RS, Herschman HR. In vivo glucocorticoids regulate cyclooxygenase- 1 but not cyclooxygenase- 1 in peritoneal macrophages. J Pharmacol Exp Ther. 1994;270:1340–4.

    PubMed  CAS  Google Scholar 

  14. Mertz PM, DeWitt DL, Steller-Stevenson WG, Wahl LM. Interleukin 10 suppression of monocyte prostaglandin H synthase-2. J Biel Chem. 1994;269:21322–9.

    CAS  Google Scholar 

  15. Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Lee L, Isakson PC. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Nat! Acad Sci USA. 1994;91:12013–17.

    Article  PubMed  CAS  Google Scholar 

  16. Masferrer JL, Zweifel BS, Manning PT, Hauser S, Leahy KM, Smith WG, Isakson PC, Seibert K. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc Nat! Acad Sci USA. 1994;91:3228–32.

    Article  PubMed  CAS  Google Scholar 

  17. Morham SC, Langenbach R, Loftin CD, Tiano HF et a1. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell. 1995;83:473–82.

    Article  PubMed  CAS  Google Scholar 

  18. Langenbach R, Morham SG, Tiano HF, Loftin CD, et al. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell. 1995;83:483–92.

    Article  PubMed  CAS  Google Scholar 

  19. Martich GD, Boujoukos AJ, Suffredini AF. Response of man to endotoxin. Immunobiology. 1993;187:403–16.

    Article  PubMed  CAS  Google Scholar 

  20. Suffredini AF, Fromm E, Parker MM et al. The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med. 1989;321:280–7.

    Article  PubMed  CAS  Google Scholar 

  21. Michie HR, Maogue PC, Spriggs DR, Revhaug A et al. Detection of circulating tumour necrosis factor after endotoxin administration. N Engl J Med. 1988;318:1481–6.

    Article  PubMed  CAS  Google Scholar 

  22. Cassale TB, Ballas ZK, Kaliner MA, Keahey TM. The effects of intravenous endotoxin on various host effector molecules. J Allergy Clin Immunol. 1990;85:45–51.

    Article  Google Scholar 

  23. Suffredini AF, Harpel PC, Parillo JE. Promotion and subsequent inhibition of plasminogen activator after administration of intravenous endotoxin to normal subjects. N Engl J Med. 1989; 320:1165–72.

    Article  PubMed  CAS  Google Scholar 

  24. Rodrick ML, Moss NM, Grbic JT et al. Effects of endotoxin infusions on the in vitro cellular immune responses in humans. J Clin Immunol. 1992;12:440–50.

    Article  PubMed  CAS  Google Scholar 

  25. Spins GA, Bloesch D, Keller U, Zimmerli W, Cammisuli S. Pretreatment with ibuprofen augments circulating tumour necrosis factor a, interleukin-6, and elastase during acute endotoxaemia. J Infect Dis. 1991;163:89–95.

    Article  Google Scholar 

  26. Martich GD, Parker MM, Cunnion RE, Suffredini AF. Effects of ibuprofen and pentoxifylline on the cardiovascular response of normal humans to endotoxin. J Appl Physiol. 1992;73:925–31

    PubMed  CAS  Google Scholar 

  27. FitzGerald GA, Brash AR. Blair IA, Lawson J. Analysis of urinary metabolites of thromboxane and prostacyclin by negative ion chemical ionization gas chromatography-mass spectrometry. In: Hayaishi O, Yamamoto S, eds. Advances in Prostaglandin, Thromboxane and Leukotriene Research. New York: Raven Press, 1985:87–90.

    Google Scholar 

  28. Catella F, Johnson JM, FitzGerald GA. Quantitative analysis of eicosanoids by gas chromatography-mass spectrometry. In: Samuelsson BB, Berti F, Folco G, Velo GP, editors. Prostanoids and Drugs. New York: Plenum Press (NATO ASI Series). 1989:15–22.

    Chapter  Google Scholar 

  29. Harris RC, McKanna JA, Akai Y, Jacobson HR, Dubois RN, Breyer MD. Cyclooxygenase 2 is associated with the macula densa of rat kidney and increases with salt restriction. J Clin Invest. 1994;94:2504–10.

    Article  PubMed  CAS  Google Scholar 

  30. O’Sullivan MG, Huggins EM, Meade EA, DeWitt D, McCall CE. Lipopolysaccharide induces prostaglandin H synthase 2 in alveolar macrophages. Biochem Biophys Res Commun. 1992; 187:1123–7.

    Article  PubMed  Google Scholar 

  31. Lee SH, Soyoola E, Chanmugam P, Hart S, et al. Selective expression of mitogen inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem. 1992;267: 25934–8.

    PubMed  CAS  Google Scholar 

  32. Van der Poll T, Van Deventer SJ, Buller HR, et al. Comparison of the early dynamics of systemic prostacyclin release after administration of tumour necrosis factor and endotoxin to healthy humans. J Infect Dis. 1991;164:599–601.

    Article  PubMed  Google Scholar 

  33. Pedersen AK, Watson M, FitzGerald GA. Inhibition of thromboxane synthase in serum: limitations of the measurement of immunoreactive 6 keto-PGF1α. Thrombosis Res. 1983;33:99–103.

    Article  Google Scholar 

  34. Wright SD, Ramos PS, Tobias RJ, Ulevitch RJ, Mathison JC. CD 14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 190;249:1431.

    Google Scholar 

  35. Leeuwenberg JF, Dentener MA, Buurman WA. Lipopolysaccharide LPS-mediated soluble TNR receptor release and TNF receptor expression by monocytes. J Immunol. 1994;152:5070–6.

    PubMed  CAS  Google Scholar 

  36. Vane JR, Botting RM. A better understanding of anti-inflammatory drugs based on isoforms of cyclooxygenase (COX-1 and COX-2). Adv Pros Thromb Leuk Res. 1995;23:41–8.

    CAS  Google Scholar 

  37. Hempel SL, Monick MM, Hunninghake GW. Lipopolysaccharide induces prostaglandin H synthase 2 protein and mRNA in human alveolar macrophages and blood monocytes. J Clin Invest. 1994; 93:391–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. B. F. McAdam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. A. Fitzgerald
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. LSU Neuroscience Center, Louisiana State University Medical Center, School of Medicine, New Orleans, LA, 70112, USA

    Nicolas Bazan

  2. The William Harvey Research Institute, St Bartholomew’s Hospital Medical College, Charterhouse Square, London, EC1M 6BQ, UK

    Jack Botting  & John Vane  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

McAdam, B.F., Fitzgerald, G.A. (1996). Enzymatic regulation of the prostaglandin response in a human model of inflammation. In: Bazan, N., Botting, J., Vane, J. (eds) New Targets in Inflammation. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5386-7_13

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-5386-7_13

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6265-7

  • Online ISBN: 978-94-011-5386-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation