Jmjd3-mediated epigenetic regulation of inflammatory cytokine gene expression in serum amyloid A-stimulated macrophages.
Jmjd3-mediated epigenetic regulation of inflammatory cytokine gene expression in serum amyloid A-stimulated macrophages.
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Jmjd3 介导的血清淀粉样蛋白 A 刺激的巨噬细胞中炎症细胞因子基因表达的表观遗传调控。
DOI：
10.1016/j.cellsig.2014.03.025
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发表时间：
2014-09
影响因子：
4.8
通讯作者：
Ye RD
中科院分区：
文献类型：
--
作者：
Yan Q;Sun L;Zhu Z;Wang L;Li S;Ye RD
血清淀粉样蛋白A（SAA）是一种主要的急性时相蛋白，在分离的吞噬细胞和滑膜成纤维细胞中具有强的类胡萝卜素活性。SAA诱导的促炎细胞因子基因表达需要转录因子如NF-κB;然而，相关的表观遗传调控机制尚不清楚。在这里，我们报告说，Jmjd 3，组蛋白H3赖氨酸27（H3 K27）去甲基化酶，是高度可诱导的SAA刺激的巨噬细胞，并在炎症细胞因子基因的诱导中发挥重要作用。SAA诱导的Jmjd 3表达导致H3 K27三甲基化减少。Jmjd 3表达的沉默显著抑制SAA诱导的促炎细胞因子包括IL-23 p19、G-CSF和TREM-1的表达，沿着上调其启动子上的H3 K27三甲基化水平。耗尽Jmjd 3表达还减弱了腹膜炎模型中促炎细胞因子基因的释放，并改善了SAA刺激小鼠的嗜中性粒细胞。最后，我们观察到，Jmjd 3是必不可少的SAA增强的巨噬细胞泡沫细胞形成氧化LDL。总之，这些结果说明了SAA刺激的巨噬细胞中促炎细胞因子基因表达的Jmjd 3依赖性表观遗传调控机制。这种机制可能会受到无菌炎症和动脉粥样硬化的治疗干预。
Serum amyloid A (SAA), a major acute-phase protein, has potent cytokine-like activities in isolated phagocytes and synovial fibroblasts. SAA-induced proinflammatory cytokine gene expression requires transcription factors such as NF-κB; however, the associated epigenetic regulatory mechanism remains unclear. Here we report that Jmjd3, a histone H3 lysine 27 (H3K27) demethylase, is highly inducible in SAA-stimulated macrophages and plays an important role in the induction of inflammatory cytokine genes. SAA-induced Jmjd3 expression leads to reduced H3K27 trimethylation. Silencing of Jmjd3 expression significantly inhibited SAA-induced expression of proinflammatory cytokines including IL-23p19, G-CSF and TREM-1, along with up-regulation of H3K27 trimethylation levels on their promoters. Depletion of Jmjd3 expression also attenuated the release of proinflammatory cytokine genes in a peritonitis model and ameliorated neutrophilia in SAA-stimulated mice. Finally, we observed that Jmjd3 is essential for SAA-enhanced macrophage foam cell formation by oxidized LDL. Taken together, these results illustrate a Jmjd3-dependent epigenetic regulatory mechanism for proinflammatory cytokine gene expression in SAA-stimulate macrophages. This mechanism may be subject to therapeutic intervention for sterile inflammation and atherosclerosis.
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影响因子：
64.5
作者：
Chen, Zhongzhou;Zang, Jianye;Zhang, Gongyi
通讯作者：
Zhang, Gongyi
DOI：
10.1016/j.bbrc.2005.03.069
发表时间：
2005-05-13
影响因子：
3.1
作者：
Lee, HY;Kim, MK;Bae, YS
通讯作者：
Bae, YS
影响因子：
64.8
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
4.4
作者：
He, Rong;Shepard, Larry W.;Ye, Richard D.
通讯作者：
Ye, Richard D.
尖端：TLR2是急性阶段血清淀粉样蛋白A的功能受体。
DOI：
10.4049/jimmunol.181.1.22
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cheng N;He R;Tian J;Ye PP;Ye RD
通讯作者：
Ye RD