title: IL-33 induces Egr-1-dependent TSLP expression via the MAPK pathways in human keratinocytes.
abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which T-helper type 2 (Th2)-type immune responses are dominant. Th2 cytokine, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) have been suggested to have an important role in AD. IL-33 is highly expressed in AD, but its role in AD has not yet been fully understood. To further identify the role of IL-33 in AD, we investigated the expression of TSLP induced by IL-33 in keratinocytes. This study revealed that IL-33 induced TSLP expression in human keratinocytes. Early growth response protein 1 (Egr)-1, which is an inflammatory transcriptional factor, is induced by IL-33. IL-33-mediated TSLP induction in keratinocytes was suppressed by treatment with mitogen-activated protein kinase (MAPK) inhibitors or small interfering RNA against Egr-1. Chromatin immunoprecipitation (ChIP) assay indicated the direct involvement of Egr-1 in IL-33-mediated TSLP induction. Taken together, these findings indicate that IL-33 may increase TSLP expression through an Egr-1-dependent mechanism via ERK1/2, JNK and p38 activation in keratinocytes. These data suggest that the IL-33-ERK/JNK/p38/Egr-1/TSLP axis is involved in allergic skin Th2 inflammation, and it may be a novel therapeutic target.
authors.affiliation: Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Woo-In
authors.initials: WI
authors.lastname: Ryu
authors.affiliation: Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Bae
authors.affiliation: Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Ryu
authors.affiliation: Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Son
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000209:etiology / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D006801:Humans; D000067596:Interleukin-33 / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D000094632:Thymic Stromal Lymphopoietin
keywords: atopic dermatitis; early growth response protein 1; interleukin-33; mitogen-activated protein kinase; thymic stromal lymphopoietin