Thromb Haemost 1995; 74(06): 1511-1515
DOI: 10.1055/s-0038-1649974
Original Articles
Fibrinolysis
Schattauer GmbH Stuttgart

Modulation of Urokinase-type Plasminogen Activator Gene Expression by Inflammatory Cytokines in Human pre-B Lymphoma Cell Line RC-K8

Authors

  • Kenji Niiya

    1   The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
  • Masahiro Shinbo

    2   The Second Department of Surgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
  • Tetsuo Ozawa

    1   The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
  • Yumiko Hayakawa

    1   The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
  • Nobuo Sakuragawa

    1   The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Further Information

Publication History

Received 24 May 1995

Accepted after resubmission 21 August 1995

Publication Date:
10 July 2018 (online)

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Summary

We examined the effects of inflammatory cytokines, such as interleukin-lα (IL-lα), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), transforming growth factor-β (TGFβ) and lipopolysaccharide (LPS), on the urokinase-type plasminogen activator (uPA) gene expression in RC-K8 human pre-B lymphoma cells. Recombinant IL-1α, recombinant IL-1β and LPS but not recombinant IL-6, recombinant TNFα and TGFβ dose-dependently increased uPA accumulation in the conditioned medium. Northern blot analysis revealed that uPA mRNA levels rapidly increased with a peak induction at 2 h after stimulation with IL-lα and IL-1β, but uPA mRNA increase by LPS began at 9 h after stimulation and the increase was maintained until the experiment ended at 24 h. These responses were independent of de novo synthesis, rather amplified in the presence of a protein synthesis inhibitor. The effects by IL-1α and IL-1β were prevented by addition of anti-IL-1α and anti-IL-1β neutralizing antibodies, respectively. In contrast, both antibodies did not prevent LPS-induced uPA gene expression. Therefore, it is unlikely that the effect by LPS is through induction of IL-1. Both IL-1α and IL-1 β rapidly activated uPA gene transcription, but not increased stability of uPA mRNA. These results suggest that both IL-1α and IL-1 β cause a rapid activation of uPA gene transcription in which de novo protein synthesis is not required and that LPS induces uPA gene expression independently of the IL-1 pathway. These modulations of uPA production by inflammatory mediators may be implicated in tumor growth and metastasis.