Egr-1 is a key regulator of IL-17A-induced psoriasin upregulation in psoriasis

Exp Dermatol. 2014 Dec;23(12):890-5. doi: 10.1111/exd.12554.

Abstract

The early growth response (Egr)-1 is a transcriptional factor which plays an important role in the regulation of cell growth, differentiation, cell survival and immune responses. Emerging evidences including our data demonstrate that the Egr-1 expression is up-regulated in the psoriatic skin lesions. The purpose of this study was to investigate the significance and regulatory mechanism of Egr-1 in the pathogenesis of psoriasis. Through microarray analysis, we found out that psoriasin (S100A7) expression was increased in the Egr-1 overexpressed cells. Our results showed that IL-17A increased Egr-1 expression in the skin of psoriatic patients and cultured human keratinocytes. We then investigated activation of mitogen-activated protein kinase as an upstream signal regulator of Egr-1 expression. IL-17A-induced Egr-1 expression was suppressed by ERK inhibitor. In addition, IL-17A induced psoriasin expression in cultured keratinocytes and the skin of IL-17A intradermally injected mouse. IL-17A-mediated psoriasin upregulation was reduced after treatment of small interfering RNAs against Egr-1. Furthermore, the results of chromatin immunoprecipitation assays demonstrated that Egr-1 directly binds the psoriasin promoter. Our findings present a novel signalling mechanism by which IL-17A can induce the Egr-1-dependent psoriasin expression via the ERK pathway in human keratinocytes. This study suggests that Egr-1 may be a novel and important modulator in IL-17A-mediated immune response in psoriasis.

Keywords: Egr-1; IL-17A; keratinocytes; psoriasin; psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Early Growth Response Protein 1 / antagonists & inhibitors
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Female
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Interleukin-17 / metabolism*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred BALB C
  • Psoriasis / etiology*
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • S100 Calcium Binding Protein A7
  • S100 Proteins / genetics*
  • Up-Regulation

Substances

  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • IL17A protein, human
  • Interleukin-17
  • S100 Calcium Binding Protein A7
  • S100 Proteins
  • S100A7 protein, human
  • S100a7a protein, mouse