Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Aug;80(2):333–340. doi: 10.1172/JCI113077

Analysis of prostaglandin E2 effect on T lymphocyte activation. Abrogation of prostaglandin E2 inhibitory effect by the tumor promotor 12.0 tetradecanoyl phorbol-13 acetate.

S Chouaib, R J Robb, K Welte, B Dupont
PMCID: PMC442242  PMID: 3038954

Abstract

We have investigated the inhibitory potential of prostaglandin E2 (PGE2) with respect to intracellular messengers implicated in the signaling system of T-lymphocyte activation pathway. Using the fluorescent indicator Quin 2, it is demonstrated that PGE2 inhibits the increase in cytosolic-free calcium concentration [Ca2+]i. Reconstitution of calcium mobilization in the presence of PGE2 by the calcium ionophore A23187 results in a partial restoration of both interleukin 2 (IL2) production and cell proliferation and has no effect on the inhibition of transferrin receptor expression. In contrast, the treatment of cell cultures with the tumor promotor 12.0 tetra decanoyl phorbol-13-acetate (TPA) abrogates the suppressor activity of PGE2. When T lymphocyte stimulation is provided by the combination of A23187 and TPA, the PGE2 inhibitory effect does not occur. These data also indicate that the down regulation of transferrin receptor by PGE2 is proximal to protein kinase C activation and is not associated with decreased expression of the functional IL2 receptor.

Full text

PDF
333

Selected References

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

  1. Ashwell J. D., Robb R. J., Malek T. R. Proliferation of T lymphocytes in response to interleukin 2 varies with their state of activation. J Immunol. 1986 Oct 15;137(8):2572–2578. [PubMed] [Google Scholar]
  2. Butcher R. W., Baird C. E. Effects of prostaglandins on adenosine 3',5'-monophosphate levels in fat and other tissues. J Biol Chem. 1968 Apr 25;243(8):1713–1717. [PubMed] [Google Scholar]
  3. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  4. Chouaib S., Chatenoud L., Klatzmann D., Fradelizi D. The mechanisms of inhibition of human IL 2 production. II. PGE2 induction of suppressor T lymphocytes. J Immunol. 1984 Apr;132(4):1851–1857. [PubMed] [Google Scholar]
  5. Chouaib S., Fradelizi D. The mechanism of inhibition of human IL 2 production. J Immunol. 1982 Dec;129(6):2463–2468. [PubMed] [Google Scholar]
  6. Chouaib S., Welte K., Mertelsmann R., Dupont B. Prostaglandin E2 acts at two distinct pathways of T lymphocyte activation: inhibition of interleukin 2 production and down-regulation of transferrin receptor expression. J Immunol. 1985 Aug;135(2):1172–1179. [PubMed] [Google Scholar]
  7. Farrar W. L., Anderson W. B. Interleukin-2 stimulates association of protein kinase C with plasma membrane. Nature. 1985 May 16;315(6016):233–235. doi: 10.1038/315233a0. [DOI] [PubMed] [Google Scholar]
  8. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  9. Goodwin J. S., Bankhurst A. D., Messner R. P. Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell. J Exp Med. 1977 Dec 1;146(6):1719–1734. doi: 10.1084/jem.146.6.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goodwin J. S., Ceuppens J. Regulation of the immune response by prostaglandins. J Clin Immunol. 1983 Oct;3(4):295–315. doi: 10.1007/BF00915791. [DOI] [PubMed] [Google Scholar]
  11. Goodwin J. S., Messner R. P., Bankhurst A. D., Peake G. T., Saiki J. H., Williams R. C., Jr Prostaglandin-producing suppressor cells in Hodgkin's disease. N Engl J Med. 1977 Nov 3;297(18):963–968. doi: 10.1056/NEJM197711032971802. [DOI] [PubMed] [Google Scholar]
  12. Hesketh T. R., Smith G. A., Houslay M. D., Warren G. B., Metcalfe J. C. Is an early calcium flux necessary to stimulate lymphocytes? Nature. 1977 Jun 9;267(5611):490–494. doi: 10.1038/267490a0. [DOI] [PubMed] [Google Scholar]
  13. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kantor H. S., Hampton M. Indomethacin in submicromolar concentrations inhibits cyclic AMP-dependent protein kinase. Nature. 1978 Dec 21;276(5690):841–842. doi: 10.1038/276841a0. [DOI] [PubMed] [Google Scholar]
  15. Mills G. B., Cheung R. K., Grinstein S., Gelfand E. W. Increase in cytosolic free calcium concentration is an intracellular messenger for the production of interleukin 2 but not for expression of the interleukin 2 receptor. J Immunol. 1985 Mar;134(3):1640–1643. [PubMed] [Google Scholar]
  16. Neckers L. M., Cossman J. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3494–3498. doi: 10.1073/pnas.80.11.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Neefe J. R., Curl G. R., Woody J. N. Absolute requirement for adherent cells in the production of human interleukin 2 (IL2). Cell Immunol. 1981 Sep 1;63(1):71–80. doi: 10.1016/0008-8749(81)90029-0. [DOI] [PubMed] [Google Scholar]
  18. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  19. Rittenhouse-Simmons S. Production of diglyceride from phosphatidylinositol in activated human platelets. J Clin Invest. 1979 Apr;63(4):580–587. doi: 10.1172/JCI109339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Robb R. J., Greene W. C., Rusk C. M. Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen. J Exp Med. 1984 Oct 1;160(4):1126–1146. doi: 10.1084/jem.160.4.1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Robb R. J., Munck A., Smith K. A. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981 Nov 1;154(5):1455–1474. doi: 10.1084/jem.154.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sasportes M., Wollman E., Cohen D., Carosella E., Bensussan A., Fradelizi D., Dausset J. Suppression of the human allogenetic response in vitro with primed lymphocytes and suppressive supernates. J Exp Med. 1980 Aug 1;152(2 Pt 2):270s–283s. [PubMed] [Google Scholar]
  23. Smith K. A., Cantrell D. A. Interleukin 2 regulates its own receptors. Proc Natl Acad Sci U S A. 1985 Feb;82(3):864–868. doi: 10.1073/pnas.82.3.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Snyder D. S., Beller D. I., Unanue E. R. Prostaglandins modulate macrophage Ia expression. Nature. 1982 Sep 9;299(5879):163–165. doi: 10.1038/299163a0. [DOI] [PubMed] [Google Scholar]
  25. Steeg P. S., Johnson H. M., Oppenheim J. J. Regulation of murine macrophage Ia antigen expression by an immune interferon-like lymphokine: inhibitory effect of endotoxin. J Immunol. 1982 Dec;129(6):2402–2406. [PubMed] [Google Scholar]
  26. Sutherland R., Delia D., Schneider C., Newman R., Kemshead J., Greaves M. Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4515–4519. doi: 10.1073/pnas.78.7.4515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Takai Y., Kishimoto A., Iwasa Y., Kawahara Y., Mori T., Nishizuka Y. Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids. J Biol Chem. 1979 May 25;254(10):3692–3695. [PubMed] [Google Scholar]
  28. Takai Y., Kishimoto A., Kikkawa U., Mori T., Nishizuka Y. Unsaturated diacylglycerol as a possible messenger for the activation of calcium-activated, phospholipid-dependent protein kinase system. Biochem Biophys Res Commun. 1979 Dec 28;91(4):1218–1224. doi: 10.1016/0006-291x(79)91197-5. [DOI] [PubMed] [Google Scholar]
  29. Tsien R. Y. New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry. 1980 May 27;19(11):2396–2404. doi: 10.1021/bi00552a018. [DOI] [PubMed] [Google Scholar]
  30. Tsien R. Y., Pozzan T., Rink T. J. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol. 1982 Aug;94(2):325–334. doi: 10.1083/jcb.94.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tsien R. Y., Pozzan T., Rink T. J. T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes. Nature. 1982 Jan 7;295(5844):68–71. doi: 10.1038/295068a0. [DOI] [PubMed] [Google Scholar]
  32. Uchiyama T., Broder S., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol. 1981 Apr;126(4):1393–1397. [PubMed] [Google Scholar]
  33. Welte K., Wang C. Y., Mertelsmann R., Venuta S., Feldman S. P., Moore M. A. Purification of human interleukin 2 to apparent homogeneity and its molecular heterogeneity. J Exp Med. 1982 Aug 1;156(2):454–464. doi: 10.1084/jem.156.2.454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Whitney R. B., Sutherland R. M. Enhanced uptake of calcium by transforming lymphocytes. Cell Immunol. 1972 Sep;5(1):137–147. doi: 10.1016/0008-8749(72)90091-3. [DOI] [PubMed] [Google Scholar]
  35. Wolf M., LeVine H., 3rd, May W. S., Jr, Cuatrecasas P., Sahyoun N. A model for intracellular translocation of protein kinase C involving synergism between Ca2+ and phorbol esters. Nature. 1985 Oct 10;317(6037):546–549. doi: 10.1038/317546a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES