title: Sulforaphane epigenetically regulates innate immune responses of porcine monocyte-derived dendritic cells induced with lipopolysaccharide.
abstract: Histone acetylation, regulated by histone deacetylases (HDACs) is a key epigenetic mechanism controlling gene expressions. Although dendritic cells (DCs) are playing pivotal roles in host immune responses, the effect of epigenetic modulation of DCs immune responses remains unknown. Sulforaphane (SFN) as a HDAC inhibitor has anti-inflammatory properties, which is used to investigate the epigenetic regulation of LPS-induced immune gene and HDAC family gene expressions in porcine monocyte-derived dendritic cells (moDCs). SFN was found to inhibit the lipopolysaccharide LPS induced HDAC6, HDAC10 and DNA methyltransferase (DNMT3a) gene expression, whereas up-regulated the expression of DNMT1 gene. Additionally, SFN was observed to inhibit the global HDAC activity, and suppressed moDCs differentiation from immature to mature DCs through down-regulating the CD40, CD80 and CD86 expression and led further to enhanced phagocytosis of moDCs. The SFN pre-treated of moDCs directly altered the LPS-induced TLR4 and MD2 gene expression and dynamically regulated the TLR4-induced activity of transcription factor NF-κB and TBP. SFN showed a protective role in LPS induced cell apoptosis through suppressing the IRF6 and TGF-ß1 production. SFN impaired the pro-inflammatory cytokine TNF-α and IL-1ß secretion into the cell culture supernatants that were induced in moDCs by LPS stimulation, whereas SFN increased the cellular-resident TNF-α accumulation. This study demonstrates that through the epigenetic mechanism the HDAC inhibitor SFN could modulate the LPS induced innate immune responses of porcine moDCs.
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Xueqi
authors: X
authors: Qu
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Maren
authors: M
authors: Pröll
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Christiane
authors: C
authors: Neuhoff
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Rui
authors: R
authors: Zhang
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany; Department of Animal Science, Faculty of Agriculture, Erciyes University, 38039 Kayseri, Turkey.
authors: Mehmet Ulas
authors: MU
authors: Cinar
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany; Department of Animal Breeding and Genetics, Faculty of Animal Husbandry, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh.
authors: Md Munir
authors: MM
authors: Hossain
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Dawit
authors: D
authors: Tesfaye
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Christine
authors: C
authors: Große-Brinkhaus
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Dessie
authors: D
authors: Salilew-Wondim
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Ernst
authors: E
authors: Tholen
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Christian
authors: C
authors: Looft
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Michael
authors: M
authors: Hölker
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Karl
authors: K
authors: Schellander
authors: Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors: Muhammad Jasim
authors: MJ
authors: Uddin
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002457:Cell Extracts; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics*; D017879:Isothiocyanates / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides; D034421:Sus scrofa; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D002457:Cell Extracts; D016207:Cytokines; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013454:Sulfoxides; D051197:Toll-Like Receptor 4; D014157:Transcription Factors; D004248:DNA (Cytosine-5-)-Methyltransferases; D006655:Histone Deacetylases; C016766:sulforaphane