TY - JOUR
T1 - Platelet-activating factor induces epigenetic modifications in human mast cells
AU - Damiani, Elisabetta
AU - Puebla-Osorio, Nahum
AU - Gorbea, Enrique
AU - Ullrich, Stephen E
N1 - Funding Information:
This work was supported by a grant from the National Cancer Institute (CA131207) and the Cancer Prevention and Research Institute of Texas (RP120777). The histology, characterized cell line core, DNA methylation analysis core, and flow cytometry facilities at the MDACC are supported in part by a core grant from the NCI (CA16672). We thank Nasser Kazimi and Francesca Brugè for technical support, and Dr Haiyan Li for help with the ChIP assays.
Publisher Copyright:
© 2015 The Society for Investigative Dermatology.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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 epigenetic modifications. We suggest that PAF may serve as an endogenous molecular mediator that links the environment (UV radiation) with the epigenome.
AB - 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 epigenetic modifications. We suggest that PAF may serve as an endogenous molecular mediator that links the environment (UV radiation) with the epigenome.
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U2 - 10.1038/jid.2015.336
DO - 10.1038/jid.2015.336
M3 - Article
C2 - 26316070
AN - SCOPUS:84948719684
SN - 0022-202X
VL - 135
SP - 3034
EP - 3040
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 12
ER -