Airways Disease Section, National Heart & Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK.
J Inflamm (Lond). 2011 Jan 27;8(1):1. doi: 10.1186/1476-9255-8-1.
Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD) to study the expression of acetylated histones (H) 3 and 4 in inflamed mucosa. Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K) 8 and 12 in contrast to non-inflamed tissue. In addition, acetylated H4 was localised to inflamed tissue and to Peyer's patches (PP) in dextran sulfate sodium (DSS)-treated rat models. Within the PP, H3 acetylation was detected in the mantle zone whereas H4 acetylation was seen in both the periphery and the germinal centre. Finally, acetylation of H4 was significantly upregulated in inflamed biopsies and PP from patients with CD. Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.
组蛋白的翻译后修饰，特别是乙酰化，与炎症基因表达的调节有关。我们使用两种肠道炎症的动物模型和克罗恩病（CD）患者的活检样本，研究了乙酰化组蛋白（H）3 和 4 在炎症黏膜中的表达。在三硝基苯磺酸结肠炎模型中，炎症黏膜中组蛋白 H4 的乙酰化显著升高，特别是在赖氨酸残基（K）8 和 12 上，与非炎症组织相比。此外，在葡聚糖硫酸钠（DSS）处理的大鼠模型中，乙酰化的 H4 定位于炎症组织和派尔集合淋巴结（PP）。在 PP 中，H3 乙酰化在套区检测到，而 H4 乙酰化在边缘区和生发中心都可见。最后，在 CD 患者的炎症活检和 PP 中，H4 的乙酰化显著上调。在 PP 中观察到 H4K5 和 K16 的乙酰化增强。这些结果表明组蛋白乙酰化与炎症有关，可能为黏膜炎症提供一个新的治疗靶点。
