Augmentation of ultraviolet B radiation-induced tumor necrosis factor production by the epidermal platelet-activating factor receptor

Lady C. Dy, Yong Pei, Jeffrey B. Travers

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Ultraviolet B radiation (UVB) has been shown to damage human keratinocytes in part by inducing oxidative stress and cytokine production. Indeed, UVB-indueed production of the pro-inflammatory and cytotoxie cytokine tumor necrosis factor α (TNF-α) has been implicated in the epidermal damage seen in response to acute solar radiation. Though the lipid mediator platelet-activating factor (PAF) is synthesized in response to oxidative stress, and keratinocytes express PAF receptors linked to cytokine biosynthesis, it is not known whether PAF is involved in UVB-induced epidermal cell cytokine production. These studies examined the role of the PAF system in UVB-induced epidermal cell TNF-α biosynthesis using a novel model system created by retrovital-mediated transduction of the PAF receptor- negative human epidermal cell line KB with the human PAF receptor (PAF-R). Treatment of PAF-R-expressing KB cells with the metabolically stable PAF-R agonist carbamoyl-PAF resulted in increased TNF-α mRNA and protein, indicating that activation of the epidermal PAF-R was linked to TNF-α production. UVB irradiation of PAF-R-expressing KB cells resulted in significant increases in both TNF-α mRNA and protein in comparison to UVB- treated control KB cells. However, UVB treatment up-regulated cyclooxygenase- 2 mRNA levels to the same extent in both PAF-R-expressing and control KB cells. Pretreatment with the antioxidant vitamin E or the PAF-R antagonists WEB 2086 and A-85783 inhibited UVB-induced TNF-α production in the PAF-R- positive but not control KB cells. These studies suggest that the epidermal PAF-R may be a pharmacological target for UVB in skin.

Original languageEnglish (US)
Pages (from-to)26917-26921
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number38
DOIs
StatePublished - Sep 17 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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