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; Tetsuo Takeuchi; Makoto Kobayashi; Isao Miyoshi; Tomohiro Hayashi; Nobuo Sakuragawa

doi:10.1055/s-0038-1646396

Thrombosis and Haemostasis, Table of Contents

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

Abstract

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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.

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References

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