Document Detail


Signal transduction pathways involved in the stimulation of tissue type plasminogen activator by interleukin-1alpha and Porphyromonas gingivalis in human osteosarcoma cells.
MedLine Citation:
PMID:  16953813     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-1alpha (IL-1alpha) 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-1alpha 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-1alpha 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-1alpha or P. gingivalis-stimulated t-PA production, respectively (p < 0.05). CONCLUSIONS: Our findings demonstrated that IL-1alpha 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.
Authors:
Yu-Chao Chang; Yung-Chuan Ho; Lin Shin-Shen Chou; Ming-Yung Chou; Fu-Mei Huang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of periodontal research     Volume:  41     ISSN:  0022-3484     ISO Abbreviation:  J. Periodont. Res.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-06     Completed Date:  2006-11-29     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0055107     Medline TA:  J Periodontal Res     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  374-80     Citation Subset:  D; IM    
Affiliation:
Department of Periodontics, Chung Shan Medical University Hospital, Taichung, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors,  physiology
Butadienes / pharmacology
Caseins / metabolism*
Cell Line, Tumor
Chromones / pharmacology
Culture Media, Conditioned
Electrophoresis, Polyacrylamide Gel
Enzyme Inhibitors / pharmacology
Humans
Imidazoles / pharmacology
Interleukin-1alpha / physiology*
MAP Kinase Kinase Kinases / antagonists & inhibitors,  physiology
MAP Kinase Signaling System* / drug effects,  physiology
Morpholines / pharmacology
Nitriles / pharmacology
Osteosarcoma
Porphyromonas gingivalis / physiology*
Pyridines / pharmacology
Tissue Plasminogen Activator / antagonists & inhibitors,  biosynthesis*
Up-Regulation / drug effects
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  physiology
Chemical
Reg. No./Substance:
0/Butadienes; 0/Caseins; 0/Chromones; 0/Culture Media, Conditioned; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Interleukin-1alpha; 0/Morpholines; 0/Nitriles; 0/Pyridines; 0/SB 203580; 0/U 0126; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.11.25/MAP Kinase Kinase Kinases; EC 3.4.21.68/Tissue Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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