Examination of the signal transduction pathways leading to activation of gelatinolytic activity by interleukin-1alpha and Porphyromonas gingivalis in human osteosarcoma cells.

doi:10.1111/j.1600-0765.2004.00720.x

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 期刊論文 > Item 310902500/11532

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题名:	Examination of the signal transduction pathways leading to activation of gelatinolytic activity by interleukin-1alpha and Porphyromonas gingivalis in human osteosarcoma cells.
作者:	Chang, Yu-Chao Chu, Shu-Chen Yang, Shun-Fa Hsieh, Yih-Shou Yang, Li-Chiu Huang, Fu-Mei
贡献者:	中山醫學大學
日期:	2004
上传时间:	2015-07-22T05:30:06Z (UTC)
ISSN:	0022-3484
摘要:	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. The purpose of this study was to investigate the gelatinolytic activity in human osteosarcoma cells stimulated with interleukin-1alpha (IL-1alpha) 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]. IL-1alpha 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. 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-1alpha or P. gingivalis. In addition, SB203580, U0126, and LY294002 significantly reduced the IL-1alpha 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). Our findings demonstrated that IL-1alpha 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.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/11532 http://dx.doi.org/10.1111/j.1600-0765.2004.00720.x
關聯:	J Periodontal Res 2004 Jun;39(3):168-74
显示于类别:	[生化微生物免疫研究所] 期刊論文

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