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

Sang Hoon Jeong, Hee Joo Kim, Yeonsue Jang, Woo In Ryu, Hana Lee, Jin Hee Kim, Hyun Cheol Bae, Jae Eun Choi, Young Chul Kye, Sang Wook Son

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7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)890-895
Number of pages6
JournalExperimental Dermatology
Volume23
Issue number12
DOIs
Publication statusPublished - 2014 Jan 1

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ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Biochemistry

Cite this

Jeong, S. H., Kim, H. J., Jang, Y., Ryu, W. I., Lee, H., Kim, J. H., Bae, H. C., Choi, J. E., Kye, Y. C., & Son, S. W. (2014). Egr-1 is a key regulator of IL-17A-induced psoriasin upregulation in psoriasis. Experimental Dermatology, 23(12), 890-895. https://doi.org/10.1111/exd.12554