title: Egr-1 is a key regulator of IL-17A-induced psoriasin upregulation in psoriasis.
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.
authors.affiliation: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Jeong
authors.forename: Hee Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yeonsue
authors.initials: Y
authors.lastname: Jang
authors.forename: Woo In
authors.initials: WI
authors.lastname: Ryu
authors.forename: Hana
authors.initials: H
authors.lastname: Lee
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Bae
authors.forename: Jae Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Kye
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Son
mesh_terms: D000818:Animals; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C508717:IL17A protein, human; D020381:Interleukin-17; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; C506174:S100a7a protein, mouse
keywords: Egr-1; IL-17A; keratinocytes; psoriasin; psoriasis