Modulation of urokinase-type plasminogen activator gene expression by inflammatory cytokines in human pre-B lymphoma cell line RC-K8
| Autor: | Tetsuo Ozawa, Kenji Niiya, Nobuo Sakuragawa, Yumiko Hayakawa, Masahiro Shinbo |
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| Rok vydání: | 1995 |
| Předmět: |
Lipopolysaccharides
Lymphoma B-Cell Alpha (ethology) Biology Gene Expression Regulation Enzymologic Proinflammatory cytokine Antigen-Antibody Reactions Transforming Growth Factor beta TGF beta signaling pathway Tumor Cells Cultured Humans Northern blot Beta (finance) Cells Cultured Regulation of gene expression Interleukin-6 Tumor Necrosis Factor-alpha Hematology Molecular biology Urokinase-Type Plasminogen Activator Gene Expression Regulation Neoplastic Cytokines Tumor necrosis factor alpha Plasminogen activator Precancerous Conditions Interleukin-1 |
| Zdroj: | Thrombosis and haemostasis. 74(6) |
| ISSN: | 0340-6245 |
| Popis: | We examined the effects of inflammatory cytokines, such as interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), transforming growth factor-beta (TGF beta) and lipopolysaccharide (LPS), on the urokinase-type plasminogen activator (uPA) gene expression in RC-K8 human pre-B lymphoma cells. Recombinant IL-1 alpha, recombinant IL-1 beta and LPS but not recombinant IL-6, recombinant TNF alpha and TGF beta 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-1 alpha and IL- 1 beta, 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-1 alpha and Il-1 beta were prevented by addition of anti-IL-1 alpha and anti-IL-1 beta 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-1 alpha and IL- 1 beta rapidly activated uPA gene transcription, but not increased stability of uPA mRNA. These results suggest that both IL-1 alpha and IL-1 beta 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. |
| Databáze: | OpenAIRE |
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