Epigenetic regulation of human β-defensin 2 and CC chemokine ligand 20 expression in gingival epithelial cells in response to oral bacteria.
Gingival epithelia utilize multiple signaling pathways to regulate innate immune responses to various oral bacteria, but little is understood about how these bacteria alter epithelial epigenetic status. In this study we report that DNA methyltransferase (DNMT1) and histone deacetylase expression were decreased in gingival epithelial cells treated with oral pathogen Porphyromonas gingivalis and nonpathogen Fusobacterium nucleatum. Pretreatment with trichostatin A and sodium butyrate, which increase acetylation of chromatin histones, significantly enhanced the gene expression of antimicrobial proteins human β-defensin 2 (hBD2) and CC chemokine ligand 20 (CCL20) in response to both bacterial challenges. Pretreatment with DNMT inhibitor 5'-azacytidine increased hBD2 and CCL20 expression in response to F. nucleatum, but not to P. gingivalis. Furthermore, we observed a differential pattern of protein levels of H3K4me3, which has been associated with chromatin remodeling and activation of gene transcription, in response to P. gingivalis vs. F. nucleatum. This study provides a new insight into the bacteria-specific innate immune responses via epigenetic regulation.
Department of Oral Biology, University of Washington, Seattle, Washington, USA. leiyin@u.washington.edu
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D016866:Bacteroidaceae Infections / Q000276:immunology*; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000276:immunology; D019175:DNA Methylation / Q000276:immunology; D057890:Epigenomics; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D016967:Fusobacterium nucleatum / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D005881:Gingiva / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000276:immunology; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000276:immunology; D006657:Histones / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000378:metabolism; D008745:Methylation; D016966:Porphyromonas gingivalis / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
D054418:Chemokine CCL20; D002843:Chromatin; C106641:DEFB4A protein, human; D006657:Histones; D016209:Interleukin-8; D012333:RNA, Messenger; D023083:beta-Defensins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
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