Parasar Bibudha, Chang Pamela V
Department of Chemistry and Chemical Biology , Cornell University , Ithaca , NY 14853 , USA.
Department of Microbiology and Immunology , Cornell University , 930 Campus Road, VMC C4-185 , Ithaca , NY 14853 , USA . Email:
Chem Sci. 2017 Feb 1;8(2):1450-1453. doi: 10.1039/c6sc03702j. Epub 2016 Oct 21.
The immune system is an essential component of host defense against pathogens and is largely mediated by inflammatory molecules produced by immune cells, such as macrophages. These inflammatory mediators are regulated at the transcriptional level by chromatin-modifying enzymes including histone deacetylases (HDACs). Here we describe a strategy to regulate inflammation and immunity with photocontrolled HDAC inhibitors, which can be selectively delivered to target cells by UV irradiation to minimize off-target effects. We strategically photocaged the active moiety of an HDAC inhibitor and showed that mild UV irradiation leads to the selective release of the inhibitor in a spatiotemporal manner. This methodology was used to decrease the amount of pro-inflammatory mediators produced by a subpopulation of macrophages. Our approach could ultimately be used to control inflammation as a therapeutic for inflammatory diseases, while minimizing off-target effects to healthy tissues.
免疫系统是宿主抵御病原体的重要组成部分，主要由免疫细胞（如巨噬细胞）产生的炎症分子介导。这些炎症介质在转录水平上由包括组蛋白脱乙酰酶（HDACs）在内的染色质修饰酶调节。在这里，我们描述了一种用光控HDAC抑制剂调节炎症和免疫的策略，该抑制剂可以通过紫外线照射选择性地递送至靶细胞，以尽量减少脱靶效应。我们巧妙地对HDAC抑制剂的活性部分进行了光笼化处理，并表明温和的紫外线照射会导致抑制剂以时空方式选择性释放。该方法用于减少巨噬细胞亚群产生的促炎介质的量。我们的方法最终可用于控制炎症，作为治疗炎症性疾病的一种疗法，同时尽量减少对健康组织的脱靶效应。
