[Effect of ERK1/2 signal pathway on the proliferation of lung fibroblast activated by SiO₂].
OBJECTIVE
To observe the effect of ERK1/2 signal pathway activated by SiO₂ in the proliferation of human embryonic lung fibroblast mediated by silicotic alveolar macrophages.


METHODS
The alveolar macrophages (AM) harvested from silicotic sufferers by bronchoalveolar lavage (BAL) were interacted with SiO₂ suspension once more. HELF, pretreated with the inhibitor PD98059 (50 µmol/L) for 1 hour, were stimulated by conditional supernatant fluid of silicotic sufferers. The experimentation have been classificated four group: blank group, AM control group, SiO₂ treatment group, PD98059 intervention group. The proliferation activity and expressions of Phospho-ERK1/2 of lung fibroblast activated by AM supernatant fluids of silicotic are detected with the MTT assay, flow cytometry and Western blot method after being pretreatmented with PD98059.


RESULTS
The A values of cell proliferation in SiO₂ treatment group and AM control group are 2.6 and 2.0 times that of blank group, in which the difference was statistically significant (P < 0.05). Comparing with SiO₂ treatment group, the A values of every concentrations of PD98059 intervention group decreased with a dose-response relationship, after 10, 25 and 50 µmol/L PD98059 intervention. The 25 and 50 µmol/L PD98059 intervention group were 72.1% and 48.5% of SiO₂ treatment group, which the difference is statistic (P < 0.05). The expression of phospho-ERK1/2 in SiO₂ treatment group was up, which appeared in 15 min and apparent activated in 30 min (A value is 0.4653 ± 0.0265), and then still in the higher state afterwards declined after 60 min. In addition to 15 min, the expression of phospho-ERK1/2 protein in SiO₂ treatment group at each time point are 1.25, 1.23, 1.25 times over the same period AM control group respectively, the differences were statistically significant (P < 0.05).


CONCLUSIONS
The silicotic supernatant of alveolar macrophages have promote proliferation of HELF and activation of ERK1/2, which may involve in the development of silicosis pathogenesis by ERK1/2 signal pathway.
Department of Pathology of North China Coal Medical College, Tangshan, Hebei Province, China.
Li
L
Feng
Xian-hua
XH
Wang
Hai-bing
HB
Peng
D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012822:Silicon Dioxide / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D005419:Flavonoids; D012822:Silicon Dioxide; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one