Premium
Examination of the signal transduction pathways leading to activation of gelatinolytic activity by interleukin‐1α and Porphyromonas gingivalis in human osteosarcoma cells
Author(s) -
Chang YuChao,
Chu ShuChen,
Yang ShunFa,
Hsieh YihShou,
Yang LiChiu,
Huang FuMei
Publication year - 2004
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.1600-0765.2004.00720.x
Subject(s) - porphyromonas gingivalis , signal transduction , interleukin , osteosarcoma , immunology , cancer research , microbiology and biotechnology , chemistry , periodontitis , biology , medicine , cytokine
Background: Recently, evidence show that matrix metalloproteinases (MMP) play an important role in the pathogenesis of periodontal diseases. However, the mechanisms and signal transduction pathways involved in the production of MMPs in human osteosarcoma cells are not fully understood. Objectives: The purpose of this study was to investigate the gelatinolytic activity in human osteosarcoma cells stimulated with interleukin‐1α (IL‐1α) or Porphyromonas gingivalis in the absence or presence of SB203580 (p38 inhibitor), U0126 [mitogen‐activated protein kinase kinase (MEK) inhibitor], and LY294002 [phosphatidylinositaol 3‐kinase (PI3K) inhibitor]. Methods: IL‐1α and the supernatants of P. gingivalis were used to evaluate gelatinolytic activity in human osteosarcoma cells using gelatin zymography. Furthermore, to search possible signal transduction pathways, SB203580, U0126, and LY294002 were added to test how they modulated the gelatinolytic activity. Results: Gelatin zymography demonstrated that the latent proforms of gelatinases MMP‐2 and MMP‐9 were released by human osteosarcoma cells. Secretion of MMP‐9 was time‐dependent by stimulating with IL‐1α or P. gingivalis . In addition, SB203580, U0126, and LY294002 significantly reduced the IL‐1α or P. gingivalis ‐stimulated MMP‐9 production, respectively ( p < 0.05). However, none of the kinase inhibitors affected the MMP‐2 level compared with the control during the 4‐day culture period ( p > 0.05). Conclusions: Our findings demonstrated that IL‐1α and P. gingivalis enhance MMP‐9 production in human osteosarcoma cells, and the signal transduction pathways p38, MEK, and PI3K are involved in the inhibition of MMP‐9. SB203580, U0126, and LY294002 suppress MMP‐9 production and/or activity and may therefore be valuable therapeutics in MMP‐mediated periodontal destruction, and might be proved clinically useful agents, in combination with standard treatment modalities, in the treatment of periodontitis.