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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

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
› Author Affiliations
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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.

 

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