Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases.
Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases.
复制标题
螺旋藻提取物通过组蛋白脱乙酰基酶调节螺旋藻提取物的抗炎作用。
DOI：
10.3390/nu8060381
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发表时间：
2016-06-21
期刊：
影响因子：
5.9
通讯作者：
Lee JY
中科院分区：
文献类型：
--
作者：
Pham TX;Park YK;Lee JY
我们以前证明了螺旋藻（SPE）的有机提取物，一种可食用的蓝绿藻，具有有效的抗炎作用。在这项研究中，我们研究了组蛋白去乙酰化酶（hdac）的调节是否在巨噬细胞SPE的抗炎作用中起作用。用SPE处理巨噬细胞后，HDAC2、3和4蛋白迅速且剂量依赖性地降低，随后HDAC2、3和4蛋白mRNA水平下降。在钙蛋白酶抑制剂、溶酶体酸化抑制剂和Ca2+/钙调素依赖性蛋白激酶II的存在下，HDAC4蛋白的降解被减弱，而蛋白酶体抑制剂则没有。在spe处理的巨噬细胞中，乙酰化组蛋白H3升高至与泛hdac抑制剂处理的巨噬细胞相似的水平，同时在LPS刺激下抑制炎症基因表达。敲低HDAC3增加了基础和脂多糖诱导的促炎基因表达，而敲低HDAC4增加了白细胞介素-1β (IL-1β)的基础表达，但减弱了脂多糖诱导的炎症基因表达。染色质免疫沉淀显示，SPE降低了Il-1β和肿瘤坏死因子α (Tnfα)启动子上p65结合和H3K9/K14乙酰化。我们的研究结果表明，SPE通过促进HDAC蛋白降解，增加了整体组蛋白H3乙酰化，但降低了组蛋白H3K9/K14乙酰化和p65在Il-1β和Tnfα启动子上的结合，从而发挥其抗炎作用。
We previously demonstrated that the organic extract of Spirulina platensis (SPE), an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs) play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca2+/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β), but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα) promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect.