In Vivo and In Vitro Silica Induces Nuclear Factor Egr-1 Activation Mediated by ERK 1/2 in RAW264.7 Cell Line.

ABSTRACT

The transcription factor early growth response gene (Egr-1) is a stress response gene activated by various forms of stress. The effect of silica on transcription and expression of Egr-1 was investigated in rat lung and in RAW264.7 cells. Silica induced the expression of Egr-1 in vivo and was mainly located in alveolar macrophage cells and lung epithelial cells. Furthermore, silica induced Egr-1 mRNA and protein expression in cultured RAW264.7 cells. Immunofluorescence microscopy revealed translocation of Egr-1 to the nucleus in response to silica. The contribution of the extracellular signal-regulated kinase (ERK) pathway to the activation of Egr-1 in response to silica was examined. Exposure to silica resulted in a rapid phosphorylation of ERK 1/2 kinases in RAW264.7 cells. MAP Kinase Kinase (MEK) inhibitor U0126 prevented Egr-1 induction by silica. The results suggest that silica could induce Egr-1 activation in macrophages in vivo and in vitro and that phosphorylated ERK 1/2 may be involved in this action.