IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors.
IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors.
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IRF5 在儿童期 SLE 中升高，并受组蛋白乙酰转移酶和组蛋白脱乙酰酶抑制剂调节
DOI：
10.18632/oncotarget.17586
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发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Zhou GP
中科院分区：
文献类型：
--
作者：
Shu J;Li L;Zhou LB;Qian J;Fan ZD;Zhuang LL;Wang LL;Jin R;Yu HG;Zhou GP
干扰素调节因子5（Interferon Regulatory Factor 5，IRF 5）在诱导I型干扰素、促炎细胞因子和趋化因子中起关键作用，并参与系统性红斑狼疮（Systemic Lupus Erythematosus，SLE）等自身免疫性疾病的发病机制。然而，IRF 5和儿童期发作的SLE之间的关系仍然难以捉摸。在本研究中，我们证明了IRF 5，IFN-α和Sp1的mRNA表达水平在儿童期发病的SLE中显著增加，如定量实时PCR所示，Sp1和IFN-α的表达与IRF 5呈正相关。除了用作抗肿瘤药物外，许多组蛋白脱乙酰酶抑制剂（HDACi）还显示出有效的抗炎特性;然而，它们对IRF 5表达的影响仍不清楚。在这项研究中，我们发现HDACi抑制素A（TSA）和组蛋白乙酰转移酶（HAT）-p300下调IRF 5启动子活性，mRNA表达和蛋白质水平，而HAT-p300/CBP相关因子没有影响。TSA还能抑制THP-1细胞产生TNF-α和IL-6。此外，染色质免疫沉淀试验显示，TSA抑制Sp1、RNA聚合酶II、HDAC 3和p300与IRF 5核心启动子区域的DNA结合。我们的研究结果表明，HDACi可能通过抑制IRF 5的表达，对自身免疫性疾病如SLE患者具有治疗潜力。
Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5. In addition to being used as antitumor drugs, a number of histone deacetylase inhibitors (HDACi) display potent anti-inflammatory properties; however, their effects on IRF5 expression remain unclear. In this study, we identified that HDACi trichostatin A (TSA) and histone acetyltransferase (HAT)-p300 downregulated IRF5 promoter activity, mRNA expression, and protein level, whereas the HAT-p300/CBP-associated factor had no effect. Moreover, TSA inhibited the production of TNF-α and IL-6 in differentiated THP-1cells. Furthermore, chromatin immunoprecipitation assays revealed that TSA inhibited DNA binding of Sp1, RNA polymerase II, HDAC3, and p300 to the core promoter region of IRF5. Our results suggest that HDACi may have therapeutic potential in patients with autoimmune diseases such as SLE through repression of IRF5 expression.
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影响因子：
20.3
作者：
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影响因子：
27.4
作者：
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Reedquist KA
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作者：
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