title: UVB induces HIF-1α-dependent TSLP expression via the JNK and ERK pathways.
abstract: Thymic stromal lymphopoietin (TSLP) may have a key role in the initiation and maintenance of allergic inflammatory diseases, including atopic dermatitis. The present study revealed that UVB radiation exposure could induce TSLP expression in human keratinocytes and a human skin equivalent model. In addition, we investigated the regulatory mechanism of UVB-induced TSLP expression in keratinocytes. TSLP expression was upregulated by transfection with pcDNA3-hypoxia-inducible factor (HIF)-1α (P402A and P564A), which stably expresses HIF-1α protein. UVB-induced TSLP induction in keratinocytes was suppressed in the treatment of mitogen-activated protein kinase inhibitors or small interfering RNAs against HIF-1α. The results of chromatin immunoprecipitation assays indicate the direct involvement of HIF-1α in UVB-mediated TSLP induction. Taken together, these findings indicate that UVB exposure may increase TSLP expression through a HIF-1α-dependent mechanism via the c-JUN N-terminal kinase and extracellular signal-regulated kinase pathways in human keratinocytes. Our data showed that UVB-induced TSLP might increase secretion of the T-helper type 2-attracting chemokine (c-c motif) ligand 17 by human dendritic cells. The present study suggests an important role of HIF-1α in UVB-mediated immune response in keratinocytes.
authors: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea; Department of Biochemistry, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors: Yeonsue
authors: Y
authors: Jang
authors: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors: Sang H
authors: SH
authors: Jeong
authors: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors: Yoon-Hee
authors: YH
authors: Park
authors: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors: Hyun C
authors: HC
authors: Bae
authors: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors: Hana
authors: H
authors: Lee
authors: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors: Woo-In
authors: WI
authors: Ryu
authors: Department of Biochemistry, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors: Gil H
authors: GH
authors: Park
authors: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, Korea. Electronic address: skin4u@korea.ac.kr.
authors: Sang W
authors: SW
authors: Son
mesh_terms: D002461:Cell Line, Transformed; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D015870:Gene Expression / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D000860:Hypoxia / Q000276:immunology / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000094632:Thymic Stromal Lymphopoietin