UVB induces HIF-1α-dependent TSLP expression via the JNK and ERK pathways

J Invest Dermatol. 2013 Nov;133(11):2601-2608. doi: 10.1038/jid.2013.203. Epub 2013 May 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Transformed
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / radiation effects
  • Gene Expression / immunology
  • Gene Expression / radiation effects
  • Humans
  • Hypoxia / immunology
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / immunology
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • Keratinocytes / radiation effects*
  • MAP Kinase Signaling System / immunology*
  • Promoter Regions, Genetic / physiology
  • Thymic Stromal Lymphopoietin
  • Ultraviolet Rays
  • Up-Regulation / immunology

Substances

  • Cytokines
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Thymic Stromal Lymphopoietin