[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.

Method: 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.

Result: 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).

Conclusion: 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.