The Platelet-activating Factor Receptor Protects Epidermal Cells from Tumor Necrosis Factor (TNF) α and TNF-related Apoptosis-inducing Ligand-induced Apoptosis through an NF-κB-dependent Process

Michael D. Southall, Jason S. Isenberg, Harikrishna Nakshatri, Qiaofang Yi, Yong Pei, Dan F. Spandau, Jeffrey B. Travers

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

A number of chemical mediators can induce human keratinocytes and epidermal-derived carcinomas to undergo apoptosis, or programmed cell death. Recent evidence suggests pro-inflammatory cytokines, such as interleukin-1β or transforming growth factor α, protects carcinomas from numerous pro-apoptotic stimuli. Platelet-activating factor (1-alkyl-2-acetyl-3-glycerophosphocholine; PAF) is a lipid mediator with pro-inflammatory effects on numerous cell types. Although PAF can be metabolized to other bioactive lipids, the majority of PAF effects occur through activation of a G protein-coupled receptor. Using a model system created by retroviral transduction of the PAF receptor (PAF-R) into the PAF-R-negative human epidermal cell line KB and the PAF-R-expressing keratinocyte cell line HaCaT, we now demonstrate that activation of the epidermal PAF-R results in protection from apoptosis induced by tumor necrosis factor (TNF) α or TNF-related apoptosis-inducing ligand. The PAF-mediated protection was inhibited by PAF-R antagonists, and protection did not occur in PAF-R-negative KB cells. Additionally, we show protection from TNFα- or TRAIL-induced apoptosis by PAF-R activation is dependent on the transcription factor nuclear factor (NF)κB, because PAF-R activation-induced NF-κB and epidermal cells transduced with a super-repressor form of inhibitor κB were not protected by the PAF-R. These studies provide a mechanism whereby the epidermal PAF-R, and possibly other G protein-coupled receptors, can exert anti-apoptotic effects through an NFκB-dependent process.

Original languageEnglish (US)
Pages (from-to)45548-45554
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number49
DOIs
StatePublished - Dec 7 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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