[Silicon dioxide-upregulated plasminogen activators inhibitor-1 protein expression is dependent on activation of extracellular signal-regulated kinase/activator protein-1 signaling pathway].
OBJECTIVE
To investigate the role of extracellular signal-regulated kinase (ERK)/activator protein-1 (AP-1) signaling pathway in SiO(2)-induced plasminogen activators inhibitor-1 (PAI-1) protein expression in human lung epithelial cells A549.


METHODS
A549 cells were cultured and then stimulated with 200 microg/ml SiO(2) for 0 approximately 24 h. To prevent AP-1 activity, Curcumin was added into culture medium before incubating with SiO(2) and transient TAM-67 transfection was performed. In addition, PD98059 was pretreated with cells to prevent ERK activity. The PAI-1 protein expression and ERK activity were evaluated by Western blot. The AP-1 DNA binding activity was tested by EMSA.


RESULTS
(1) At 4, 8 and 16 h after exposure to SiO(2), the fold change of AP-1 DNA binding activity (relative to the control group) were 1.3, 1.3, and 2.1, respectively (P < 0.05). 10, 25, 50 micromol/L Curcumin inhibited SiO(2)-induced PAI-1 protein expression (inhibition ratio: 20%, 63%, 65%; P < 0.05). TAM-67 downregulated SiO(2)-induced PAI-1 protein expression (inhibition ratio: 59%, P < 0.05). (2) SiO(2) activated ERK and PD98059 downregulated SiO(2)-induced PAI-1 protein expression (inhibition ratio: 51%, P < 0.05). (3) PD98059 downregulated SiO(2)-induced AP-1 DNA binding activity (inhibition ratio: 73%, P < 0.05).


CONCLUSIONS
ERK/AP-1 signaling pathway is responsible for SiO(2)-induced PAI-1 protein expression.
Li
Xiang
X
Department of pathology Xiangya SCHOOL OF Medicine, Central South UNIVERSITY. Changsha 410013, China.
Hu
Yong-Bin
YB
Peng
Jin-Wu
JW
D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000633:toxicity*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D018808:Transcription Factor AP-1; D012822:Silicon Dioxide; D048049:Extracellular Signal-Regulated MAP Kinases