Thromb Haemost 1991; 66(02): 232-238
DOI: 10.1055/s-0038-1646396
Review Article
Schattauer GmbH Stuttgart

Dexamethasone and Phorbol Ester, but not Cytokines, Increase the Production of Plasminogen Activator Inhibitor Type-2 in the PL-21 Human Promyelocytic Leukemia Cell Line

Kenji Niiya
The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama
,
Tetsuo Takeuchi
*   Department of Medicine, Kochi Medical School, Kochi, Japan
,
Makoto Kobayashi
*   Department of Medicine, Kochi Medical School, Kochi, Japan
,
Isao Miyoshi
*   Department of Medicine, Kochi Medical School, Kochi, Japan
,
Tomohiro Hayashi
The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama
,
Nobuo Sakuragawa
The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama
› Author Affiliations
Further Information

Publication History

Received 29 May 1990

Accepted 06 February 1991

Publication Date:
25 July 2018 (online)

Summary

PL-21 is a promyelocytic leukemia cell line that produces plasminogen activator inhibitor 2 (PAI-2). Differentiation-linked expression of PAI-2 was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid (RA), dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-α (TNF-a), transforming growth factor-β (TGF-β), granulocyte-colony stimulating factor (G-CSF), and interleukin-6 (IL-6)] into the culture medium of PL-21 cells. PAI-1 and PAI-2 antigens were measured by an enzyme-linked immunoassay. The PAI-1 antigen, however, became detectable only after stimulation. The presence of PAI-2 antigen was further verified by immunoblotting using a monoclonal antibody against PAI-2 purified from a PL-21 culture medium. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amount of the latter in the culture medium and in the cell lysate was approximately 10 times and 2,500 times, as much, respectively, as that of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI-2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-a and IL-6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity. Glucocorticoid has various effects on the fibrinolytic system because it has been also shown that the mRNA of PAI-2 in a human fibrosarcoma cell line decreases in response to Dex.

 
  • References

  • 1 Carell R, Travis J. α1-antitrypsin and the serpins: Variation and countervariation. Trends Biochem Sci 1985; 10: 20-4
  • 2 Kawano T, Morimoto K, Uemura Y. Urokinase inhibitor in human placenta. Nature 1986; 217: 253-4
  • 3 Golder JP, Stephens RW. Minactivin: A human monocyte product which specifically inactivates urokinase-type plasminogen activators. Eur J Biochem 1983; 136: 517-22
  • 4 Vassalli JD, Dayer JM, Wohlwend A, Belin D. Concomitant secretion of prourokinase and of a plasminogen activator-specific inhibitor by cultured human monocytes-macrophages. J Exp Med 1984; 159: 1653-68
  • 5 Kopitar M, Rozman B, Babnik J, Turk V, Mullins DE, Wun T-C. Human leukocyte urokinase inhibitor-purification, characterization and comparative studies against different plasminogen activators. Thromb Haemostas 1985; 54: 750-5
  • 6 Littlefield BA, Johnston LJ, Manzer DS, Roche PC. Glucocorticoid inhibitor of urokinase-like plasminogen activators in cultured human lymphoblasts. Endocrinology 1985; 117: 1100-9
  • 7 Kruithof EKO, Vassalli J-D, Schleuning W-D, Mattaliano RJ, Bachmann F. Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937. J Biol Chem 1986; 261: 11207-13
  • 8 Alving BM, Krishnamurti C, Liu Y-P, Lucas DL, Wright DG. Stimulated production of urokinase and plasminogen activator inhibitor-2 by the human promyelocytic leukemia cell line HL-60. Thromb Res 1988; 51: 175-85
  • 9 Takeuchi T, Niiya K, Kubonishi I, Miyoshi I. A plasminogen activator inhibitor-2 from a promyelocytic leukemia cell line, PL-21, binds to the carboxy-terminal chain of plasminogen activators. Thromb Haemostas 1990; 63: 259-64
  • 10 Åstedt B, Lecander I, Brodin T, Lundblad A, Löw K. Purification of a specific placental plasminogen activator inhibitor by monoclonal antibody and its complex formation with plasminogen activator. Thromb Haemostas 1985; 53: 122-5
  • 11 Wun T-C, Reich E. An inhibitor of plasminogen activation from human placenta. J Biol Chem 1987; 262: 3646-53
  • 12 Medcalf RL, Van den Berg E, Schleuning W-D. Glucocorticoidmodulated gene expression of tissue- and urokinase-type plasminogen activator and plasminogen activator inhibitor 1 and 2. J Cell Biol 1988; 106: 971-8
  • 13 Lecander I, Åstedt B. Isolation of a new specific plasminogen activator inhibitor from pregnancy plasma. Br J Haematol 1986; 62: 221-8
  • 14 Wohlwend A, Belin D, Vassalli J-D. Plasminogen activator-specific inhibitors produced by human monocytes/macrophages. J Exp Med 1987; 165: 320-39
  • 15 Genton C, Kruithof EKO, Schleuning W-D. Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells. J Cell Biol 1987; 104: 705-12
  • 16 Arndt AD, Gohill J, Rankin K, Houwen B, Hart DA. Differentiation-linked expression of the plasminogen activator inhibitor type-2 gene in the human HL-60 promyelocytic cell line. Exp Cell Res 1989; 185: 473-81
  • 17 Schwartz B, Monroe MC, Bradshaw JD. Endotoxin-induced production of plasminogen activator inhibitor by human monocytes is autonomous and can be inhibited by lipid X. Blood 1989; 73: 2188-95
  • 18 Medcalf RL, Kruithof EKO, Schleuning W-D. Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin-responsive genes. J Exp Med 1988; 168: 751-9
  • 19 Sawdey M, Podor TJ, Loskutoff DJ. Regulation of type 1 plasminogen activator inhibitor gene expression in cultured bovine aortic endothelial cells. J Biol Chem 1989; 264: 10396-401
  • 20 Wilson EL, Jacobs P, Dowdle EB. The effects of dexamethasone and tetradecanoyl phorbol acetate on plasminogen activator release by human acute myeloid leukemia cells. Blood 1983; 61: 561-7
  • 21 Crutchley DJ, Conanan LB, Maynard JR. Human fibroblasts produce inhibitor directed against plasminogen activator when treated with glucocorticoids. Ann NY Acad Sci 1981; 370: 609-16
  • 22 Coleman PL, Barouski PA, Gelehrter TD. The dexamethasoneinduced inhibitor of fibrinolytic activity in hepatoma cells. A cellular product which specifically inhibits plasminogen activation. J Biol Chem 1982; 257: 4260-4
  • 23 Cwikel BJ, Barouski-Miller PA, Coleman PL, Gelehrter TD. Dexamethasone induction of an inhibitor of plasminogen activator in HTC hepatoma cells. J Biol Chem 1984; 259: 6847-51
  • 24 Collins SJ, Gallor C, Gallagher RE. Continuous growth and differentiation of human myeloild leukemia cells in suspension culture. Nature 1977; 270: 347-9
  • 25 Kubonishi I, Ohtsuki Y, Miyagi T, Yoshimoto S, Akagi T, Miyaoshi I. Electron microscopic and immunohistochemical observations of differentiation of human myeloid leukemia line, PL-21. J Cancer Res Clin Oncol 1986; 111: 203-8
  • 26 Babru S, George S, Craig C, Thomas B. Identification of interleukin-6 and TNF as two of the monocyte differentiation inducing factors in human leukocyte conditioned medium. XIVth International Symposium for Comparative Research on Leukemia and Related Diseases. Oct. 1989, Colorado, Vail. Abstract p 89.
  • 27 Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975; 256: 495-7
  • 28 Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350-4
  • 29 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (London) 1970; 227: 680-5
  • 30 Ye RD, Wun T-C, Sadler JE. cDNA cloning and expression in Escherichia coli of a plasminogen activator inhibitor from human placenta. J Biol Chem 1987; 262: 3718-25
  • 31 Webb AC, Collins KL, Snyder SE, Alexander SL, Rosenwasser LJ, Eddy RL, Shows TB, Auron PE. Human monocyte ARG-SERPIN cDNA sequence, chromosomal assignment, and homology to plasminogen activator-inhibitor. J Exp Med 1987; 166: 77-94
  • 32 Pytel BA, Peppel K, Baglioni C. Plasminogen activator inhibitor type-2 is a major protein induced in human fibroblasts and SK-MEL-109 melanoma cells by tumor necrosis factor. J Cell Physiol 1990; 144: 416-22
  • 33 Elias L, Moore PB, Rose SM. Tumor necrosis factor induced DNA fragmentation of HL-60 cells. Biochem Biophys Res Commun 1988; 157: 963-9