Silver nanoparticles induce Egr-1-dependent psoriasin expression via the ERK and p38 pathways

Background: Silver nanoparticles (Ag-NPs) can prevent bacterial infection and improve cutaneous wound healing owing to their antimicrobial activity. However, the mechanism of their antimicrobial activity is poorly understood. Aim: To determine the mechanistic relationship between Ag-NP treatment and expression of psoriasin. Methods: Human epidermal keratinocytes, neonatal (HEKn) were used. Psoriasin mRNA expression was measured by reverse transcription PCR and real-time PCR. Western blotting was performed to verify expression of early growth response-1 (Egr-1) and psoriasin, and phosphorylation of mitogen-activated protein kinase (MAPK). Psoriasin promoter activity by Egr-1 was detected by a luciferase assay. Results: Treatment of HEKn with Ag-NPs induced psoriasin mRNA and protein expression. Upregulation of psoriasin promoter activity was also observed in the luciferase assay. Ag-NPs increased Egr-1 expression, promoter activity and nuclear translocation in HEKn. Psoriasin luciferase activity was increased in HEKn transfected with Egr-1 pcDNA 3.1. Ag-NPs activated MAPK pathways including the extracellular signal-regulated kinase (ERK), p38, and c-Jun-N-terminal kinase (JNK) pathways. The upregulation of Egr-1 expression by Ag-NP stimulation was inhibited by ERK and p38 inhibitors, but not by a JNK inhibitor. Psoriasin expression was reduced in Egr-1 small interfering RNA-transfected HEKn. Conclusions: Ag-NP treatment induces upregulation of psoriasin expression through Egr-1 expression. We suggest that the ERK and p38 pathways are involved in Egr-1-dependent psoriasin expression.