Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1989 Jan;9(1):252–258. doi: 10.1128/mcb.9.1.252

Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester.

J Horiguchi 1, D Spriggs 1, K Imamura 1, R Stone 1, R Luebbers 1, D Kufe 1
PMCID: PMC362167  PMID: 2494431

Abstract

The treatment of human HL-60 promyelocytic leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcript. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNF mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase A2 blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B4. In contrast, the cyclooxygenase metabolite prostaglandin E2 inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B4 and prostaglandin E2.

Full text

PDF
252

Images in this article

253Image
on p.253
253Image
on p.253
254Image
on p.254
254Image
on p.254
255Image
on p.255
256Image
on p.256
256Image
on p.256

Selected References

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

  1. Aderem A. A., Cohen D. S., Wright S. D., Cohn Z. A. Bacterial lipopolysaccharides prime macrophages for enhanced release of arachidonic acid metabolites. J Exp Med. 1986 Jul 1;164(1):165–179. doi: 10.1084/jem.164.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asano T., Hidaka H. Vasodilatory action of HA1004 [N-(2-guanidinoethyl)-5-isoquinolinesulfonamide], a novel calcium antagonist with no effect on cardiac function. J Pharmacol Exp Ther. 1984 Oct;231(1):141–145. [PubMed] [Google Scholar]
  3. Beetens J. R., Loots W., Somers Y., Coene M. C., De Clerck F. Ketoconazole inhibits the biosynthesis of leukotrienes in vitro and in vivo. Biochem Pharmacol. 1986 Mar 15;35(6):883–891. doi: 10.1016/0006-2952(86)90072-9. [DOI] [PubMed] [Google Scholar]
  4. Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
  5. Blumberg P. M. In vitro studies on the mode of action of the phorbol esters, potent tumor promoters: part 1. Crit Rev Toxicol. 1980 Dec;8(2):153–197. doi: 10.3109/10408448009037493. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  9. Dinarello C. A., Marnoy S. O., Rosenwasser L. J. Role of arachidonate metabolism in the immunoregulatory function of human leukocytic pyrogen/lymphocyte-activating factor/interleukin 1. J Immunol. 1983 Feb;130(2):890–895. [PubMed] [Google Scholar]
  10. Feuerstein N., Cooper H. L. Rapid protein phosphorylation induced by phorbol ester in HL-60 cells. Unique alkali-stable phosphorylation of a 17,000-dalton protein detected by two-dimensional gel electrophoresis. J Biol Chem. 1983 Sep 10;258(17):10786–10793. [PubMed] [Google Scholar]
  11. Freundlich B., Trinchieri G., Perussia B., Zurier R. B. The cytotoxic effector cells in preparations of adherent mononuclear cells from human peripheral blood. J Immunol. 1984 Mar;132(3):1255–1260. [PubMed] [Google Scholar]
  12. Godfrey R. W., Johnson W. J., Hoffstein S. T. Recombinant tumor necrosis factor and interleukin-1 both stimulate human synovial cell arachidonic acid release and phospholipid metabolism. Biochem Biophys Res Commun. 1987 Jan 15;142(1):235–241. doi: 10.1016/0006-291x(87)90476-1. [DOI] [PubMed] [Google Scholar]
  13. Halenda S. P., Zavoico G. B., Feinstein M. B. Phorbol esters and oleoyl acetoyl glycerol enhance release of arachidonic acid in platelets stimulated by Ca2+ ionophore A23187. J Biol Chem. 1985 Oct 15;260(23):12484–12491. [PubMed] [Google Scholar]
  14. Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
  15. Hirata F., Schiffmann E., Venkatasubramanian K., Salomon D., Axelrod J. A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci U S A. 1980 May;77(5):2533–2536. doi: 10.1073/pnas.77.5.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Homma Y., Henning-Chubb C. B., Huberman E. Translocation of protein kinase C in human leukemia cells susceptible or resistant to differentiation induced by phorbol 12-myristate 13-acetate. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7316–7319. doi: 10.1073/pnas.83.19.7316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Horiguchi J., Warren M. K., Ralph P., Kufe D. Expression of the macrophage specific colony-stimulating factor (CSF-1) during human monocytic differentiation. Biochem Biophys Res Commun. 1986 Dec 30;141(3):924–930. doi: 10.1016/s0006-291x(86)80131-0. [DOI] [PubMed] [Google Scholar]
  18. Huang K. S., Wallner B. P., Mattaliano R. J., Tizard R., Burne C., Frey A., Hession C., McGray P., Sinclair L. K., Chow E. P. Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase. Cell. 1986 Jul 18;46(2):191–199. doi: 10.1016/0092-8674(86)90736-1. [DOI] [PubMed] [Google Scholar]
  19. Huberman E., Callaham M. F. Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1293–1297. doi: 10.1073/pnas.76.3.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Imamura K., Spriggs D., Kufe D. Expression of tumor necrosis factor receptors on human monocytes and internalization of receptor bound ligand. J Immunol. 1987 Nov 1;139(9):2989–2992. [PubMed] [Google Scholar]
  21. Kettelhut I. C., Fiers W., Goldberg A. L. The toxic effects of tumor necrosis factor in vivo and their prevention by cyclooxygenase inhibitors. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4273–4277. doi: 10.1073/pnas.84.12.4273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Koeffler H. P. Induction of differentiation of human acute myelogenous leukemia cells: therapeutic implications. Blood. 1983 Oct;62(4):709–721. [PubMed] [Google Scholar]
  23. Kramer R. M., Checani G. C., Deykin D. Stimulation of Ca2+-activated human platelet phospholipase A2 by diacylglycerol. Biochem J. 1987 Dec 15;248(3):779–783. doi: 10.1042/bj2480779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kreutter D., Caldwell A. B., Morin M. J. Dissociation of protein kinase C activation from phorbol ester-induced maturation of HL-60 leukemia cells. J Biol Chem. 1985 May 25;260(10):5979–5984. [PubMed] [Google Scholar]
  25. Kunkel S. L., Spengler M., May M. A., Spengler R., Larrick J., Remick D. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem. 1988 Apr 15;263(11):5380–5384. [PubMed] [Google Scholar]
  26. Lotem J., Sachs L. Regulation of normal differentiation in mouse and human myeloid leukemic cells by phorbol esters and the mechanism of tumor promotion. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5158–5162. doi: 10.1073/pnas.76.10.5158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mavier P., Edgington T. S. Human monocyte-mediated tumor cytotoxicity. I. Demonstration of an oxygen-dependent myeloperoxidase-independent mechanism. J Immunol. 1984 Apr;132(4):1980–1986. [PubMed] [Google Scholar]
  28. Merrill A. H., Jr, Sereni A. M., Stevens V. L., Hannun Y. A., Bell R. M., Kinkade J. M., Jr Inhibition of phorbol ester-dependent differentiation of human promyelocytic leukemic (HL-60) cells by sphinganine and other long-chain bases. J Biol Chem. 1986 Sep 25;261(27):12610–12615. [PubMed] [Google Scholar]
  29. Nakaki T., Mita S., Yamamoto S., Nakadate T., Kato R. Inhibition by palmitoylcarnitine of adhesion and morphological changes in HL-60 cells induced by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 1984 May;44(5):1908–1912. [PubMed] [Google Scholar]
  30. Nedwin G. E., Svedersky L. P., Bringman T. S., Palladino M. A., Jr, Goeddel D. V. Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J Immunol. 1985 Oct;135(4):2492–2497. [PubMed] [Google Scholar]
  31. Old L. J. Tumor necrosis factor (TNF). Science. 1985 Nov 8;230(4726):630–632. doi: 10.1126/science.2413547. [DOI] [PubMed] [Google Scholar]
  32. Pantazis P., Sariban E., Kufe D., Antoniades H. N. Induction of c-sis gene expression and synthesis of platelet-derived growth factor in human myeloid leukemia cells during monocytic differentiation. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6455–6459. doi: 10.1073/pnas.83.17.6455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Philip R., Epstein L. B. Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. Nature. 1986 Sep 4;323(6083):86–89. doi: 10.1038/323086a0. [DOI] [PubMed] [Google Scholar]
  34. Rovera G., Ferrero D., Pagliardi G. L., Vartikar J., Pessano S., Bottero L., Abraham S., Lebman D. Induction of differentiation of human myeloid leukemias by phorbol diesters: phenotypic changes and mode of action. Ann N Y Acad Sci. 1982 Dec 10;397:211–220. doi: 10.1111/j.1749-6632.1982.tb43428.x. [DOI] [PubMed] [Google Scholar]
  35. Rovera G., O'Brien T. G., Diamond L. Induction of differentiation in human promyelocytic leukemia cells by tumor promoters. Science. 1979 May 25;204(4395):868–870. doi: 10.1126/science.286421. [DOI] [PubMed] [Google Scholar]
  36. Russell S. W., Pace J. L. Gamma interferon interferes with the negative regulation of macrophage activation by prostaglandin E2. Mol Immunol. 1984 Mar;21(3):249–254. doi: 10.1016/0161-5890(84)90080-4. [DOI] [PubMed] [Google Scholar]
  37. Sakata A., Ida E., Tominaga M., Onoue K. Arachidonic acid acts as an intracellular activator of NADPH-oxidase in Fc gamma receptor-mediated superoxide generation in macrophages. J Immunol. 1987 Jun 15;138(12):4353–4359. [PubMed] [Google Scholar]
  38. Sariban E., Imamura K., Luebbers R., Kufe D. Transcriptional and posttranscriptional regulation of tumor necrosis factor gene expression in human monocytes. J Clin Invest. 1988 May;81(5):1506–1510. doi: 10.1172/JCI113482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sariban E., Luebbers R., Kufe D. Transcriptional and posttranscriptional control of c-fos gene expression in human monocytes. Mol Cell Biol. 1988 Jan;8(1):340–346. doi: 10.1128/mcb.8.1.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sariban E., Mitchell T., Kufe D. Expression of the c-fms proto-oncogene during human monocytic differentiation. Nature. 1985 Jul 4;316(6023):64–66. doi: 10.1038/316064a0. [DOI] [PubMed] [Google Scholar]
  41. Stone R. M., Sariban E., Pettit G. R., Kufe D. W. Bryostatin 1 activates protein kinase C and induces monocytic differentiation of HL-60 cells. Blood. 1988 Jul;72(1):208–213. [PubMed] [Google Scholar]
  42. Trinchieri G., Kobayashi M., Rosen M., Loudon R., Murphy M., Perussia B. Tumor necrosis factor and lymphotoxin induce differentiation of human myeloid cell lines in synergy with immune interferon. J Exp Med. 1986 Oct 1;164(4):1206–1225. doi: 10.1084/jem.164.4.1206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tsunawaki S., Nathan C. F. Release of arachidonate and reduction of oxygen. Independent metabolic bursts of the mouse peritoneal macrophage. J Biol Chem. 1986 Sep 5;261(25):11563–11570. [PubMed] [Google Scholar]
  44. Wang A. M., Creasey A. A., Ladner M. B., Lin L. S., Strickler J., Van Arsdell J. N., Yamamoto R., Mark D. F. Molecular cloning of the complementary DNA for human tumor necrosis factor. Science. 1985 Apr 12;228(4696):149–154. doi: 10.1126/science.3856324. [DOI] [PubMed] [Google Scholar]
  45. Wilson J. T., Wilson L. B., deRiel J. K., Villa-komaroff L., Efstratiadis A., Forget B. G., Weissman S. M. Insertion of synthetic copies of human globin genes into bacterial plasmids. Nucleic Acids Res. 1978 Feb;5(2):563–581. doi: 10.1093/nar/5.2.563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yamamoto S., Gotoh H., Aizu E., Kato R. Failure of 1-oleoyl-2-acetylglycerol to mimic the cell-differentiating action of 12-O-tetradecanoylphorbol 13-acetate in HL-60 cells. J Biol Chem. 1985 Nov 15;260(26):14230–14234. [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES