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Signal transduction pathways involved in the stimulation of tissue type plasminogen activator by interleukin‐1α and Porphyromonas gingivalis in human osteosarcoma cells
Author(s) -
Chang YuChao,
Ho YungChuan,
Chou Lin ShinShen,
Chou MingYung,
Huang FuMei
Publication year - 2006
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2005.00848.x
Subject(s) - ly294002 , signal transduction , porphyromonas gingivalis , microbiology and biotechnology , p38 mitogen activated protein kinases , mapk/erk pathway , kinase , plasminogen activator , chemistry , cancer research , biology , pi3k/akt/mtor pathway , endocrinology , medicine , periodontitis
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.