Actual Role of Prostaglandins in Inflammation

Summary

The prostaglandins (PGs) are a family of naturally occurring cyclopentane-containing carboxylic acids of varying degrees of unsaturation. They are produced from arachidonic acid, which is released from tissue phospholipids by the enzyme phospholipase A2. The enzyme cyclooxygenase is responsible for the conversion of free arachidonic acid into unstable cyclic peroxides (PGG2 and PGH2).

These compounds are known as PG endoperoxides and are further transformed by specific enzymes into the different PGs, notably the thromboxanes and PGI2 (epoprostenol). PGs are not prestored in tissues, but are formed when activation of phospholipase or other lipases takes place in a tissue. This activation can result from various factors such as physiological stimuli (e.g. exercise, pregnancy, age), pharmacological stimuli [e.g. angiotensin, bradykinin, noradrenaline (norepinephrine)] or pathological stimuli (tissue injury or disease). PGs exhibit a number of biological effects, primarily upon those cells immediately surrounding the site of their synthesis, partly because they are rapidly inactivated. Prostanoids have been shown to have a wide range of effects on many physiological systems and a role for PGs in tissue inflammation and injury has been proposed. Over the years, evidence of the powerful pro-inflammatory action of PGs has accumulated, nevertheless, recent findings on anti-inflammatory effects of PGs, as well as on mechanisms of action of NSAIDs, other than inhibition of PG biosynthesis suggest a modulatory role for PGs in the inflammatory process.

This is a preview of subscription content, access via your institution.

References

  1. Abramson S, Korchak H, Ludewig R, Edelson H, Haines K, et al. Modes of action of aspirin-like drugs. Proceedings of the National Academy of Sciences of the USA 82: 7227–7231, 1985

    PubMed  Article  CAS  Google Scholar 

  2. Berridge MJ. Inositol triphosphate and diacyl glycerol: two interacting second messengers. Annual Review of Biochemistry 56: 159–177, 1987

    PubMed  Article  CAS  Google Scholar 

  3. Bourne HR, Lichtenstein LM, Melmon KL. Pharmacologic control of allergic histamine release in vitro: evidence for an inhibitory role of 3′,5′-adenosine monophosphate in human leukocytes. Journal of Immunology 108: 695–705, 1970

    Google Scholar 

  4. Chilton F, Murphy RC. Remodeling of arachidonate-containing phosphoglycerides within human neutrophil. Journal of Biological Chemistry 261: 7771–7777, 1986

    PubMed  CAS  Google Scholar 

  5. Dale HH. Croonian lectures on some chemical factors in the control of the circulation. Lancet 1: 1285–1290, 1929

    Google Scholar 

  6. Davidson FF, Dennis EA, Powell M, Glenney JR. Inhibition of phospholipase A2 by ‘Lipocortins’ and Calpactins. Journal of Biological Chemistry 262: 1698–1706, 1987

    PubMed  CAS  Google Scholar 

  7. Fantone JC, Kunkel SL, Weingarten B. Inhibition of carrageenininduced rat footpad edema by systemic treatment with prostaglandin of the E series. Biochemical Pharmacology 31: 3126–3128, 1982

    PubMed  Article  CAS  Google Scholar 

  8. Fantone JC, Kunkel SL, Zurier RB. Effects of prostaglandins on in vivo, immune and inflammatory reactions. In Goodwin JS (Ed.) Prostaglandins and immunity, pp. 123–146, Martinus Nijhoff Publishing, Boston, 1985

    Google Scholar 

  9. Fantone JC, Marasco WA, Elgas LJ, Ward PA. Anti-inflammatory effects of prostaglandin E1: in vivo modulation of the formyl peptide chemotactic receptor on the rat neutrophil. Journal of Immunology 130: 1495–1497, 1983

    CAS  Google Scholar 

  10. Feldberg W, Saxena PN. Fever produced in rabbits and cats by prostaglandin E1 injected into the cerebral ventricle. Journal of Physiology 215: 23P–24P, 1971

    PubMed  CAS  Google Scholar 

  11. Ferreira SH, Nakamura M, Castro MSA. The hyperalgesic effects of prostacyclin and prostaglandin E2. Prostaglandins 16: 31–38, 1978

    PubMed  Article  CAS  Google Scholar 

  12. Flower R. Macrocortin and the mechanism of action of glucocorticoids. Advances in Inflammatory Research 7: 61–74, 1984

    CAS  Google Scholar 

  13. Hamberg M, Samuelsson B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proceedings of the National Academy of Sciences of the USA 71: 3400–3404, 1974

    PubMed  Article  CAS  Google Scholar 

  14. Hamberg M, Svensson J, Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proceedings of the National Academy of Sciences of the USA 71: 345–351, 1974

    PubMed  Article  CAS  Google Scholar 

  15. Hansen HS. 15-hydroxy prostaglandin dehydrogenase. A review. Prostaglandins 12: 647–665, 1976

    PubMed  Article  CAS  Google Scholar 

  16. Humes JL, Winter CA, Sadowski SJ, Kuehl FA. Multiple sites on prostaglandin cycloxygenase are determinant in the action of non-steroidal anti-inflammatory agents. Proceedings of the National Academy of Sciences of the USA 78: 2053–2056, 1981

    PubMed  Article  CAS  Google Scholar 

  17. Kenneth Adams III G, Lichtenstein LM. Indomethacin enhances response of human bronchus to antigen. American Review of Respiratory Disease 131: 8–10, 1985

    Google Scholar 

  18. Kunkel SL, Thrall RS, Kunkel RG, McCormick JR, Ward PA, et al. Suppression of immune-complex vasculitis in rats by prostaglandin. Journal of Clinical Investigation 64: 1525–1529, 1979

    PubMed  Article  CAS  Google Scholar 

  19. Moncada S, Vane JR. Arachidonic acid metabolites and the interactions between platelets and blood vessel walls. New England Journal of Medicine 300: 1142–1146, 1979

    PubMed  Article  CAS  Google Scholar 

  20. Mueller HV, O’Flaherty JT, Wykle RL. Ether lipid content and fatty acid distribution in rabbit polymorphonuclear neutrophil phospholipid. Lipids 13: 72–80, 1982

    Article  Google Scholar 

  21. Nakagawa Y, Sugiuro T, Waku K. The molecular species composition of diacyl-alkylacyl- and alkenylacylglycero-phospholipids in rabbit alveolar macrophages. High amounts of 1-O-hexadecyl-2-arachidonoyl molecular species in alkylacylglycer-ophosphocholine. Biochimica et Biophysica Acta 833: 323–328, 1985

    PubMed  Article  CAS  Google Scholar 

  22. Peters SP, Schulman ES, MacGlashan DW, Schleimer RP, New-ball HH, et al. Pharmacologic and biochemical studies of human lung mast cells. Journal of Allergy and Clinical Immunology 69: 150–154, 1982

    Article  Google Scholar 

  23. Raud J, Dahlen S-E, Sydbom A, Lindbom L, Hedqvist P. Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release. Proceedings of the National Academy of Sciences of the USA 85: 2315–2319, 1988

    PubMed  Article  CAS  Google Scholar 

  24. Tauber AI, Kaliner M, Stechschulte DJ, Austen KF. Immunologic release of histamine and slow reacting substance of anaphylaxis from human lung. V. Effect of prostaglandins on release of histamine. Journal of Immunology 111: 27–32, 1973

    CAS  Google Scholar 

  25. Van den Bosch H. Intracellular phospholipases A. Biochimica et Biophysica Acta 604: 191–199, 1980

    PubMed  Google Scholar 

  26. Waite M, VanDeenan LLM. Hydrolysis of phospholipids and glycerides by rat-liver preparations. Biochimica et Biophysica Acta 137: 498–507, 1967

    PubMed  Article  CAS  Google Scholar 

  27. Weissman G, Dukor P, Zurier RB. Effects of cyclic AMP on release of lysosomal enzymes from phagocytes. Nature 231: 131–135, 1971

    Google Scholar 

  28. Williams DE, Hale SE, Okita RT, Masters BSS. A prostaglandin omega-hydrolase cytochrome P-450 purified from lungs of pregnant rabbits. Journal of Biological Chemistry 259: 14600–14604, 1984

    PubMed  CAS  Google Scholar 

  29. Williams TJ, Peck MJ. Role of prostaglandin-mediated vasodilation in inflammation. Nature 270: 530–532, 1977

    PubMed  Article  CAS  Google Scholar 

  30. Yoshioka S, Nakashima S, Okano Y, Nozawa Y. Arachidonic acid mobilization among phospholipids in murine mastocytoma P-815 cells: role of ether-linked phospholipids. Journal of Lipid Research 27: 939–945, 1986

    PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Dr A. Sala.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sala, A., Folco, G. Actual Role of Prostaglandins in Inflammation. Drug Invest 3, 4–9 (1991). https://doi.org/10.1007/BF03258310

Download citation

Keywords

  • PGE2
  • PGI2
  • Epoprostenol
  • Sodium Salicylate
  • Arthus Reaction