Ultraviolet light suppresses IFN-γ-induced IL-7 gene expression in murine keratinocytes by interfering with IFN regulatory factors

Yoshinori Aragane, Agatha Schwarz, Thomas A. Luger, Kiyoshi Ariizumi, Akira Takashima, Thomas Schwarz

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

UV light is a potent stimulus for keratinocytes to release several cytokines. Recently, UV light was shown to inhibit keratinocyte release of IL-7, a growth factor for dendritic epidermal T cells. Since to date IL-7 is the only keratinocyte-derived cytokine down-regulated by UV light, we addressed the molecular mechanisms involved. IFN-γ treatment of the murine keratinocyte cell line Pam 212 resulted in an up-regulation of IL-7 mRNA, while IL-7 transcripts were suppressed in cells exposed to UV before IFN-γ. Because IFN-γ induces IL-7 via activation of an IFN-stimulated response element (ISRE) located in the 5′ upstream region of the IL-7 gene, bandshift assays were performed using the ISRE sequence from the IL-7 gene. Nuclear extracts from untreated cells revealed two bands, a slower migrating band identified by supershift analysis as IFN regulatory factor-2 (IRF-2), a transcriptional repressor, and a more rapidly migrating band identified as IRF-1, a transcriptional activator. IFN-γ significantly induced IRF-1 binding, whereas UV treatment plus IFN-γ decreased IRF-1 binding, suggesting that UV light suppresses IFN-γ-induced expression of IL-7 by interfering with IRF-1. Chloramphenicol transferase assay confirmed functional relevance, showing that the minimal promoter sequence for the ISRE explicitly responded to IFN-γ, which was suppressed by UV irradiation. Northern blot analysis using an IRF-1 cDNA probe revealed that UV light reduced IFN-γ-induced IRF-1 mRNA. This study demonstrates that UV light can inhibit cytokine artivities by interference with transcriptional activators. This newly described ability of UV light may contribute to its immunosuppressive properties.

Original languageEnglish (US)
Pages (from-to)5394-5399
Number of pages6
JournalJournal of Immunology
Volume158
Issue number11
StatePublished - Dec 1 1997

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this