Skip to main content
PMC 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
. 1977 Nov;74(11):4955–4958. doi: 10.1073/pnas.74.11.4955

Prostaglandin regulation of macrophage collagenase production.

L M Wahl, C E Olsen, A L Sandberg, S E Mergenhagen
PMCID: PMC432076  PMID: 200941

Abstract

The production of collagenase (EC 3.4.24.3) by endotoxin-stimulated macrophages was significantly inhibited by indomethacin, indicating that prostaglandins (PGs) mediate this effect. Inhibitions of collagenase production by indomethacin was overcome by addition of exogenous PGE2 at 10 nM whereas the addition of 0.1 and 1.0 micrometer PGE2 increased the enzyme production to 3 times that achieved by endotoxin. Although the addition of prostaglandin alone to macrophage cultures did not stimulate collagenase production, the simultaneous addition of PGE1 or PGE2 and endotoxin enhanced collagenase activity 2- to 10-fold. This increase was detectable at PGE concentrations of 10 nM and was optimal at 0.1-1.0 micrometer. PGF2alpha had little effect on either the enhancement of collagenase production by endotoxin-stimulated macrophages or its restoration in cultures inhibited by indomethacin. Radioimmunoassay of prostaglandins in the culture media revealed that macrophages exposed to endotoxin secreted 40-fold more PGE2 than did unstimulated cells. The increase in PGE2 was detected 4 hr after exposure to endotoxin and was maximal at 14 hr. The peak PGE2 concentrations in the culture media were similar to those of exogenous PGE2 (about 10 nM) needed to restore collagenase production in indomethacin-treated cultures. These findings demonstrate the involvement of PGE in the endotoxin-activation of macrophages with resultant production of collagenase.

Full text

PDF

Selected References

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

  1. Auletta F. J., Ausman R. M., Caldwell B. V. Development and standardization of radioimmunoassays for prostaglandins E, F, and A. Clin Chem. 1974 Dec;20(12):1580–1587. [PubMed] [Google Scholar]
  2. Beutner E. H., Triftshauser C., Hazen S. P. Collagenase activity of gingival tissue from patients with periodontal disease. Proc Soc Exp Biol Med. 1966 Apr;121(4):1082–1085. doi: 10.3181/00379727-121-30972. [DOI] [PubMed] [Google Scholar]
  3. Bray M. A., Gordon D., Morley J. Proceedings: Role of prostaglandins in reactions of cellular immunity. Br J Pharmacol. 1974 Nov;52(3):453P–453P. [PMC free article] [PubMed] [Google Scholar]
  4. Dayer J. M., Krane S. M., Russell R. G., Robinson D. R. Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells. Proc Natl Acad Sci U S A. 1976 Mar;73(3):945–949. doi: 10.1073/pnas.73.3.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fullmer H. M., Gibson W. Collagenolytic activity in gingivae of man. Nature. 1966 Feb 12;209(5024):728–729. doi: 10.1038/209728a0. [DOI] [PubMed] [Google Scholar]
  6. Gemsa D., Steggemann L., Menzel J., Till G. Release of cyclic AMP from macrophages by stimulation with prostaglandins. J Immunol. 1975 Apr;114(4):1422–1424. [PubMed] [Google Scholar]
  7. Goodson J. M., Dewhirst F. E., Brunetti A. Prostaglandin E2 levels and human periodontal disease. Prostaglandins. 1974 Apr 10;6(1):81–85. doi: 10.1016/s0090-6980(74)80043-2. [DOI] [PubMed] [Google Scholar]
  8. Gordon D., Bray M. A., Morley J. Control of lymphokine secretion by prostaglandins. Nature. 1976 Jul 29;262(5567):401–402. doi: 10.1038/262401a0. [DOI] [PubMed] [Google Scholar]
  9. Harris E. D., Jr, Krane S. M. Collagenases (first of three parts). N Engl J Med. 1974 Sep 12;291(11):557–563. doi: 10.1056/NEJM197409122911105. [DOI] [PubMed] [Google Scholar]
  10. Harris E. D., Jr, Krane S. M. Collagenases (second of three parts). N Engl J Med. 1974 Sep 19;291(12):605–609. doi: 10.1056/NEJM197409192911205. [DOI] [PubMed] [Google Scholar]
  11. Harris E. D., Jr, Krane S. M. Collagenases (third of three parts). N Engl J Med. 1974 Sep 26;291(13):652–661. doi: 10.1056/NEJM197409262911305. [DOI] [PubMed] [Google Scholar]
  12. Koopman W. J., Gillis M. H., David J. R. Prevention of MIF activity by agents known to increase cellular cyclic AMP. J Immunol. 1973 Jun;110(6):1609–1614. [PubMed] [Google Scholar]
  13. Krane S. M. Collagenase production by human synovial tissues. Ann N Y Acad Sci. 1975 Jun 13;256:289–303. doi: 10.1111/j.1749-6632.1975.tb36056.x. [DOI] [PubMed] [Google Scholar]
  14. Levine L., Hinkle P. M., Voelkel E. F., Tashjian A. H., Jr Prostaglandin production by mouse fibrosarcoma cells in culture: inhibition by indomethacin and aspirin. Biochem Biophys Res Commun. 1972 May 26;47(4):888–896. doi: 10.1016/0006-291x(72)90576-1. [DOI] [PubMed] [Google Scholar]
  15. Robinson D. R., McGuire M. B., Levine L. Prostaglandins in the rheumatic diseases. Ann N Y Acad Sci. 1975 Jun 13;256:318–329. doi: 10.1111/j.1749-6632.1975.tb36058.x. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Smith J. W., Steiner A. L., Parker C. W. Human lymphocytic metabolism. Effects of cyclic and noncyclic nucleotides on stimulation by phytohemagglutinin. J Clin Invest. 1971 Feb;50(2):442–448. doi: 10.1172/JCI106511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Stockman G. D., Mumford D. M. The effect of prostaglandins on the in vitro blastogenic response of human peripheral blood lymphocytes. Exp Hematol. 1974;2(2):65–72. [PubMed] [Google Scholar]
  19. Wahl L. M., Wahl S. M., Mergenhagen S. E., Martin G. R. Collagenase production by endotoxin-activated macrophages. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3598–3601. doi: 10.1073/pnas.71.9.3598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wahl L. M., Wahl S. M., Mergenhagen S. E., Martin G. R. Collagenase production by lymphokine-activated macrophages. Science. 1975 Jan 24;187(4173):261–263. doi: 10.1126/science.163038. [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