Platelet-Activating Factor Induces Epigenetic Modifications in Human Mast Cells

The Journal of Investigative Dermatology
Elisabetta DamianiS E Ullrich

Abstract

UV radiation-induced systemic immune suppression is a major risk factor for skin cancer induction. The migration of dermal mast cells from the skin to the draining lymph nodes has a prominent role in activating systemic immune suppression. UV-induced keratinocyte-derived platelet-activating factor (PAF) activates mast cell migration, in part by upregulating the expression of CXCR4 on the surface of mast cells. Others have indicated that epigenetic mechanisms regulate CXCR4 expression; therefore, we asked whether PAF activates epigenetic mechanisms in mast cells. Human mast cells were treated with PAF, and the effect on DNA methylation and/or acetylation was measured. PAF suppressed the expression of DNA methyltransferase (DNMT) 1 and 3b. On the other hand, PAF increased p300 histone acetyltransferase expression, and the acetylation of histone H3, which coincided with a decreased expression of the histone deacetylase HDAC2. Chromatin immunoprecipitation assays indicated that PAF treatment activated the acetylation of the CXCR4 promoter. Finally, inhibiting histone acetylation blocked p300 upregulation and suppressed PAF-induced surface expression of CXCR4. Our findings suggest a novel molecular mechanism for PAF, activation of e...Continue Reading

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Citations

Nov 17, 2015·The Journal of Investigative Dermatology·Remco van Doorn, Frank de Gruijl
Feb 6, 2017·Scientific Reports·Elisabetta DamianiStephen E Ullrich
Nov 15, 2017·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Prue H Hart, Mary Norval
Jul 6, 2017·Experimental Dermatology·Hanna SiiskonenMarcus Maurer
Jan 4, 2019·The Biochemical Journal·Elisabetta DamianiHeather M Wallace
Apr 28, 2017·Frontiers in Immunology·Gilda VarricchiFrancescopaolo Granata

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Methods Mentioned

BETA
acetylation
flow cytometry
histone acetylation
immunoprecipitation assay
Protein Assay
X-ray
Reverse Transcription
PCR
Immunoprecipitation

Software Mentioned

CFX Manager
GraphPad Prism

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