Egr‐1 is a key regulator of IL‐17A‐induced psoriasin upregulation in psoriasis. Issue 12 (December 2014)

• Record Type: Journal Article
• Authors: Jeong, Sang Hoon; Kim, Hee Joo; Jang, Yeonsue; Ryu, Woo In; Lee, Hana; Kim, Jin Hee; Bae, Hyun Cheol; Choi, Jae Eun; Kye, Young Chul; Son, Sang Wook
• Is Part Of: Experimental dermatology. Volume 23:Issue 12(2014:Dec.)
• Page Start: 890
• Page End: 895
• Publication Date: 2014-12
• Subjects: Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.12554
• Languages: English
• ISSNs: 0906-6705

Abstract

<abstract abstract-type="main" id="exd12554-abs-0001"> <title>Abstract</title> <p>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.</p> </abstract>