Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Aug;78(8):5160–5164. doi: 10.1073/pnas.78.8.5160

Mechanism of stimulation of prostaglandin synthesis by a factor from rheumatoid synovial tissue.

D R Robinson, D Bastian, P J Hamer, D M Pichiarallo, M L Stephenson
PMCID: PMC320356  PMID: 6795630

Abstract

Rheumatoid synovial cell monolayers, with [1-14C]arachidonic acid ([1-14C]AA) incorporated into cell lipids, are stimulated by a factor (RSF) produced by explant cultures of rheumatoid synovial tissue to produce up to 50-fold increases in [1-14C]prostaglandin E2 and [1-14C]prostaglandin I2. In contrast, levels of free [1-14C]AA released from RSF-stimulated cells are generally lower than [1-14C]AA levels in cultures of untreated cells. These observations are inconsistent with a mechanism of prostaglandin stimulation consisting of an increase in phospholipase activity, because this mechanism would increase free AA levels as well as prostaglandins. A mechanism is proposed in which free AA is maintained at low steady-state levels by reacylation of free AA into phospholipids at a rate more rapid than its reaction with cyclooxygenase to form prostaglandins. In this mechanism, stimulation of the rate of the cyclooxygenase step by RSF accounts for increased prostaglandin synthesis as well as the decreased release of AA. On the basis of data previously reported by others, it is suggested that this mechanism may also be applicable to the stimulation of prostaglandin synthesis by several other agents. Preliminary characterization of the RSF indicates that it is a protein, and molecular seive chromatography indicates that its molecular weight is about 18,000. The production of RSF by rheumatoid synovial tissue is suppressed to undetectable levels by 1 microM dexamethasone.

Full text

PDF
5160

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell R. M., Coleman R. A. Enzymes of glycerolipid synthesis in eukaryotes. Annu Rev Biochem. 1980;49:459–487. doi: 10.1146/annurev.bi.49.070180.002331. [DOI] [PubMed] [Google Scholar]
  2. Blackwell G. J. Phospholipase A2 and platelet aggregation. Adv Prostaglandin Thromboxane Res. 1978;3:137–142. [PubMed] [Google Scholar]
  3. Castor C. W., Dorstewitz E. L., Rowe K., Ritchie J. C. Abnormalities of connective tissue cells cultured from patients with rheumatoid arthritis. II. Defective regulation of hyaluronate and collagen formation. J Lab Clin Med. 1971 Jan;77(1):65–75. [PubMed] [Google Scholar]
  4. Castor C. W., Pek S. Connective tissue activation. XX. Stimulation of prostaglandin secretion by mediators from lymphocytes (CTAP-I) and platelets (CTAP-III). Arthritis Rheum. 1981 Mar;24(3):504–509. doi: 10.1002/art.1780240309. [DOI] [PubMed] [Google Scholar]
  5. Coughlin S. R., Moskowitz M. A., Zetter B. R., Antoniades H. N., Levine L. Platelet-dependent stimulation of prostacyclin synthesis by platelet-derived growth factor. Nature. 1980 Dec 11;288(5791):600–602. doi: 10.1038/288600a0. [DOI] [PubMed] [Google Scholar]
  6. Dayer J. M., Passwell J. H., Schneeberger E. E., Krane S. M. Interactions among rheumatoid synovial cells and monocyte-macrophages: production of collagenase-stimulating factor by human monocytes exposed to concanavalin A or immunoglobulin Fc fragments. J Immunol. 1980 Apr;124(4):1712–1720. [PubMed] [Google Scholar]
  7. Flower R. J., Blackwell G. J. The importance of phospholipase-A2 in prostaglandin biosynthesis. Biochem Pharmacol. 1976 Feb 1;25(3):285–291. doi: 10.1016/0006-2952(76)90216-1. [DOI] [PubMed] [Google Scholar]
  8. Hamerman D., Janis R., Smith C. Cartilage matrix depletion by rheumatoid synovial cells in tissue culture. J Exp Med. 1967 Dec 1;126(6):1005–1012. doi: 10.1084/jem.126.6.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hsueh W., Isakson P. C., Needleman P. Hormone selective lipase activation in the isolated rabbit heart. Prostaglandins. 1977 Jun;13(6):1073–1091. doi: 10.1016/0090-6980(77)90135-6. [DOI] [PubMed] [Google Scholar]
  10. Isakson P. C., Raz A., Denny S. E., Wyche A., Needleman P. Hormonal stimulation of arachidonate release from isolated perfused organs. Relationship to prostaglandin biosynthesis. Prostaglandins. 1977 Nov;14(5):853–871. doi: 10.1016/0090-6980(77)90302-1. [DOI] [PubMed] [Google Scholar]
  11. Kantrowitz F., Robinson D. R., McGuire M. B., Levine L. Corticosteroids inhibit prostaglandin production by rheumatiod synovia. Nature. 1975 Dec 25;258(5537):737–739. doi: 10.1038/258737a0. [DOI] [PubMed] [Google Scholar]
  12. Kunze H., Vogt W. Significance of phospholipase A for prostaglandin formation. Ann N Y Acad Sci. 1971 Apr 30;180:123–125. doi: 10.1111/j.1749-6632.1971.tb53191.x. [DOI] [PubMed] [Google Scholar]
  13. Lands W. E., Samuelsson B. Phospholipid precursors of prostaglandins. Biochim Biophys Acta. 1968 Oct 22;164(2):426–429. doi: 10.1016/0005-2760(68)90168-9. [DOI] [PubMed] [Google Scholar]
  14. Lapetina E. G., Billah M. M., Cuatrecasas P. Rapid acylation and deacylation of arachidonic acid into phosphatidic acid of horse neutrophils. J Biol Chem. 1980 Nov 25;255(22):10966–10970. [PubMed] [Google Scholar]
  15. Levine L., Hassid A. Effects of phorbol-12,13-diesters on prostaglandin production and phospholipase activity in canine kidney (MDCK) cells. Biochem Biophys Res Commun. 1977 Nov 21;79(2):477–484. doi: 10.1016/0006-291x(77)90182-6. [DOI] [PubMed] [Google Scholar]
  16. Levine L., Hassid A. Epidermal growth factor stimulates prostaglandin biosynthesis by canine kidney (MDCK) cells. Biochem Biophys Res Commun. 1977 Jun 20;76(4):1181–1187. doi: 10.1016/0006-291x(77)90980-9. [DOI] [PubMed] [Google Scholar]
  17. Meats J. E., McGuire M. B., Russell R. G. Human synovium releases a factor which stimulates chondrocyte production of PGE and plasminogen activator. Nature. 1980 Aug 28;286(5776):891–892. doi: 10.1038/286891a0. [DOI] [PubMed] [Google Scholar]
  18. Nachum R., Lipsey A., Siegel S. E. Rapid detection of gram-negative bacterial meningitis by the limulus lysate test. N Engl J Med. 1973 Nov 1;289(18):931–934. doi: 10.1056/NEJM197311012891801. [DOI] [PubMed] [Google Scholar]
  19. Needleman P., Wyche A., Bronson S. D., Holmberg S., Morrison A. R. Specific regulation of peptide-induced renal prostaglandin synthesis. J Biol Chem. 1979 Oct 10;254(19):9772–9779. [PubMed] [Google Scholar]
  20. Nijkamp F. P., Flower R. J., Moncada S., Vane J. R. Partial purification of rabbit aorta contracting substance-releasing factor and inhibition of its activity by anti-inflammatory steroids. Nature. 1976 Oct 7;263(5577):479–482. doi: 10.1038/263479a0. [DOI] [PubMed] [Google Scholar]
  21. Robinson D. R., Smith H., McGuire M. B., Levine L. Prostaglandin synthesis by rheumatoid synovium and its stimulation by colchicine. Prostaglandins. 1975 Jul;10(1):67–85. doi: 10.1016/0090-6980(75)90094-5. [DOI] [PubMed] [Google Scholar]
  22. Robinson D. R., Tashjian A. H., Jr, Levine L. Prostaglandin-stimulated bone resorption by rheumatoid synovia. A possible mechanism for bone destruction in rheumatoid arthritis. J Clin Invest. 1975 Nov;56(5):1181–1188. doi: 10.1172/JCI108195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shier W. T. Activation of high levels of endogenous phospholipase A2 in cultured cells. Proc Natl Acad Sci U S A. 1979 Jan;76(1):195–199. doi: 10.1073/pnas.76.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vonkeman H., van Dorp D. A. The action of prostaglandin synthetase on 2-arachidonyl-lecithin. Biochim Biophys Acta. 1968 Oct 22;164(2):430–432. doi: 10.1016/0005-2760(68)90169-0. [DOI] [PubMed] [Google Scholar]
  25. Whorton A. R., Smigel M., Oates J. A., Frölich J. C. Regional differences in prostacyclin formation by the kidney. Prostacyclin is a major prostaglandin of renal cortex. Biochim Biophys Acta. 1978 Apr 28;529(1):176–180. doi: 10.1016/0005-2760(78)90116-9. [DOI] [PubMed] [Google Scholar]
  26. van den Bosch H. Phosphoglyceride metabolism. Annu Rev Biochem. 1974;43(0):243–277. doi: 10.1146/annurev.bi.43.070174.001331. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES