Sulforaphane epigenetically regulates innate immune responses of porcine monocyte-derived dendritic cells induced with lipopolysaccharide.
Sulforaphane epigenetically regulates innate immune responses of porcine monocyte-derived dendritic cells induced with lipopolysaccharide.
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DOI：
10.1371/journal.pone.0121574
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Uddin MJ
中科院分区：
文献类型：
--
作者：
Qu X;Pröll M;Neuhoff C;Zhang R;Cinar MU;Hossain MM;Tesfaye D;Große-Brinkhaus C;Salilew-Wondim D;Tholen E;Looft C;Hölker M;Schellander K;Uddin MJ
组蛋白乙酰化受组蛋白脱乙酰酶(HDACs)调控，是控制基因表达的关键表观遗传机制。尽管树突状细胞(DC)在宿主免疫应答中发挥着关键作用，但表观遗传调控DC免疫应答的作用尚不清楚。萝卜硫醚(SFN)作为一种HDAC抑制剂具有抗炎作用，用于研究内毒素诱导的免疫基因和HDAC家族基因在猪单核细胞来源的树突状细胞(MoDC)中表达的表观遗传调控。SFN抑制脂多糖诱导的HDAC6、HDAC10和DNA甲基转移酶(DNMT3a)基因表达，上调DNMT1基因表达。此外，SFN还通过下调CD40、CD80和CD86的表达，抑制整体HDAC活性，抑制moDCs从未成熟向成熟DC的分化，进一步促进moDCs的吞噬功能。经MODC处理的SFN可直接改变脂多糖诱导的TLR4和MD2基因表达，并动态调节TLR4诱导的转录因子NF-κB和TBP的活性。SFN对脂多糖诱导的细胞凋亡具有保护作用，其机制可能与抑制IRF6和转化生长因子β1的产生有关。SFN可抑制内毒素刺激诱导的MODC细胞培养上清液分泌促炎细胞因子Tf-α和IL-1，而增加细胞内Tf-α的积聚。本研究表明，HDAC抑制剂SFN可通过表观遗传机制调节内毒素诱导的猪moDC的先天免疫应答。
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.
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影响因子：
3.7
作者：
Fan, Huitao;Zhang, Rui;Cinar, Mehmet Ulas
通讯作者：
Cinar, Mehmet Ulas
DOI：
10.1084/jem.20071728
发表时间：
2008-06-09
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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通讯作者：
Schutte, Brian C.
影响因子：
20.3
作者：
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