Abstract
Here, we determined the 5-hydroxymethylcytosine (5hmC), 5-methylcytosine (5mC), Ten Eleven Translocation (TETs), and DNA methyltransferases (DNMTs) levels in epithelial and inflammatory cells of labial salivary glands (LSG) from Sjögren's syndrome (SS)-patients and the effect of cytokines on HSG cells. LSG from SS-patients, controls and HSG cells incubated with cytokines were analysed. Levels of 5mC, 5hmC, DNMTs, TET2 and MeCP2 were assessed by immunofluorescence. In epithelial cells from SS-patients, an increase in TET2, 5hmC and a decrease in 5mC and MeCP2 were observed, additionally, high levels of 5mC and DNMTs and low levels of 5hmC were detected in inflammatory cells. Cytokines increased TET2 and 5hmC and decreased 5mC levels. Considering that the TET2 gene.promoter contains response elements for transcription factors activated by cytokines, together to in vitro results suggest that changes in DNA hydroxymethylation, resulting from altered levels of TET2 are likely to be relevant in the Sjögren's syndrome etiopathogenesis.
Keywords:
5-hydroxymethylcytosine; Global DNA methylation; Pro-inflammatory cytokines; Sjögren's syndrome; TET2.
Copyright © 2018 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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5-Methylcytosine / analogs & derivatives*
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5-Methylcytosine / metabolism
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Adult
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Aged
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Cytidine Deaminase / genetics
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Cytidine Deaminase / metabolism
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Cytokines / immunology
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DNA (Cytosine-5-)-Methyltransferase 1 / genetics
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DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
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DNA (Cytosine-5-)-Methyltransferases / genetics*
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DNA (Cytosine-5-)-Methyltransferases / metabolism
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DNA Methylation
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DNA Methyltransferase 3A
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DNA Methyltransferase 3B
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism
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Dioxygenases / genetics
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Dioxygenases / immunology
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Dioxygenases / metabolism
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Epigenesis, Genetic
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Female
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Gene Expression
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Gene Expression Regulation
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Humans
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Inflammation / genetics
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Inflammation / metabolism
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Lip
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Male
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Methyl-CpG-Binding Protein 2 / genetics*
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Methyl-CpG-Binding Protein 2 / metabolism
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Middle Aged
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Mixed Function Oxygenases / genetics
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Mixed Function Oxygenases / immunology
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Mixed Function Oxygenases / metabolism
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Promoter Regions, Genetic
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / immunology
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Proto-Oncogene Proteins / metabolism
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Real-Time Polymerase Chain Reaction
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Salivary Glands, Minor / cytology
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Salivary Glands, Minor / immunology
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Salivary Glands, Minor / metabolism*
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Sjogren's Syndrome / genetics*
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Sjogren's Syndrome / immunology
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Sjogren's Syndrome / metabolism
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Young Adult
Substances
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Cytokines
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DNA-Binding Proteins
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DNMT3A protein, human
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MECP2 protein, human
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Methyl-CpG-Binding Protein 2
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Proto-Oncogene Proteins
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5-hydroxymethylcytosine
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5-Methylcytosine
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Mixed Function Oxygenases
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TET1 protein, human
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TET3 protein, human
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Dioxygenases
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TET2 protein, human
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases
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DNA Methyltransferase 3A
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DNMT1 protein, human
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Cytidine Deaminase