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

Clin Exp Dermatol. 2019 Jun;44(4):390-396. doi: 10.1111/ced.13758. Epub 2018 Sep 24.

Abstract

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.

MeSH terms

  • Early Growth Response Protein 1 / drug effects
  • Early Growth Response Protein 1 / metabolism
  • Extracellular Signal-Regulated MAP Kinases / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • MAP Kinase Signaling System / drug effects
  • Metal Nanoparticles / therapeutic use*
  • RNA, Messenger / metabolism
  • S100 Calcium Binding Protein A7 / genetics*
  • Silver / pharmacology*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Early Growth Response Protein 1
  • RNA, Messenger
  • S100 Calcium Binding Protein A7
  • Silver
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases