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    Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/11335


    Title: Signal transduction pathways involved in the stimulation of tissue type plasminogen activator by interleukin-1α and Porphyromonas gingivalis in human osteosarcoma cells
    Authors: Chang, Yu-Chao
    Ho, Yung-Chuan
    Chou, Lin Shin-Shen
    Chou, Ming-Yung
    Huang, Fu-Mei
    Contributors: 中山醫學大學
    Keywords: casein zymography;human osteosarcoma cells;signal transduction pathway;tissue type plasminogen activator
    Date: 2006
    Issue Date: 2015-07-15T10:35:45Z (UTC)
    ISSN: 0022-3484
    Abstract: Background:  Recently, evidences have shown that tissue type plasminogen activator (t-PA) may play an important role in the pathogenesis of periodontal diseases. However, the mechanisms and signal transduction pathways involved in the production of t-PA in human osteosarcoma cells are not fully understood.

    Objectives:  The purpose of this study was to investigate the caseinolytic activity in human osteosarcoma cell line U2OS cells stimulated with interleukin-1α (IL-1α) or Porphyromonas gingivalis in the absence or presence of p38 inhibitor SB203580, mitogen-activated protein kinase kinase (MEK) inhibitor U0126, and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002.

    Methods:  IL-1α and the supernatants of P. gingivalis were used to evaluate the caseinolytic activity in U2OS cells by using casein zymography and enzyme-linked immunosorbent assay (ELISA). Furthermore, to search possible signal transduction pathways, SB203580, U0126, and LY294002 were added to test how they modulated the caseinolytic activity.

    Results:  Casein zymography exhibited a caseinolytic band with a molecular weight of approximately 70 kDa, suggestive of the presence of t-PA. Secretion of t-PA was found to be stimulated with IL-1α and P. gingivalis during a 2-day culture period (p < 0.05). From the results of casein zymography and ELISA, SB203580, U0126, and LY294002 significantly reduced the IL-1α or P. gingivalis-stimulated t-PA production, respectively (p < 0.05).

    Conclusions:  Our findings demonstrated that IL-1α and P. gingivalis enhance t-PA production in human osteosarcoma cells, and that the signal transduction pathways p38, MEK, and PI3K are involved in the inhibition of t-PA. SB203580, U0126, and LY294002 suppress t-PA production and/or activity and may therefore be valuable therapeutics in t-PA-mediated periodontal destruction, and might be proved clinically useful agents, in combination with standard treatment modalities, in the treatment of periodontitis.
    URI: https://ir.csmu.edu.tw:8080/ir/handle/310902500/11335
    http://dx.doi.org/10.1111/j.1600-0765.2005.00848.x
    Relation: Journal of Periodontal Research Volume 41, Issue 5, pages 374–380, October 2006
    Appears in Collections:[牙醫學系暨碩士班] 期刊論文

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