OBJECTIVETo investigate the roles of mitogen-activated protein kinases (MAPK) on silica-induced cell cycle changes.

METHODSAfter cells were treated with 200 microg/ml silica, Western blot and Immunofluorescence assays were utilized to detect the expression of cyclin D1, CDK4 and E2F-4, Flow cytometry was used to detect cell cycle progression, the dominant negative mutants techniques were used to investigate silica-induced signal pathway and the effects of which in silica-induced cell cycle changes.

RESULTSAfter cells were exposed to 200 microg/ml silica 24 h, the results of present study showed the proportion of cells in G1 phases was decreased. Silica-induced cell cycle alternation was markedly impaired by stable expression of a dominant negative mutants of ERK or JNK, but not p38. It was found that ERK and JNK were involved in silica-induced cyclin D1 and CDK4 overexpression and the decreased expression of E2F-4.

CONCLUSIONERK and JNK, but not p38, mediated silica-induced cell cycle changes in human embryo lung fibroblasts.