Department of Biology Education, College of Education, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Cell Immunol. 2010;262(1):52-7. doi: 10.1016/j.cellimm.2009.12.007. Epub 2009 Dec 29.
Once activated by infected pathogens, dendritic cells (DCs) undergo activation and release inflammatory mediators responsible for the signs of inflammation. Our aim was to elucidate whether histone deacetylase inhibitors (HDACIs), trichostatine-A (TSA), scriptaid (ST) and sodium butylate (SB) regulate the inflammatory response of DCs. Pre-treatment with TSA and ST reduced the syngeneic and allogeneic-antigen presenting activity of LPS-stimulated DCs in a dose dependent manner to statistical significance. SB also reduced the antigen presenting activity of DCs, but not significantly. HDACIs mediate their effects through the modulation of DC maturation and pre-treatment of the DCs with TSA or ST prior to treatment with LPS reduced the expressions of DC mature markers to the level of immature dendritic cells (iDCs). Moreover, TSA and ST reduced the IL-2 production from LPS-stimulated mature DCs. Our results suggest that HDACIs may actively modulate the DC-induced inflammatory response through inhibition of phenotypical or functional maturation.
一旦被感染病原体激活,树突状细胞(DCs)会经历激活并释放炎症介质,这些介质是炎症迹象的原因。我们的目的是阐明组蛋白去乙酰化酶抑制剂(HDACIs)、曲古抑菌素 A(TSA)、scriptaid(ST)和丁酸钠(SB)是否调节 DCs 的炎症反应。TSA 和 ST 的预处理以剂量依赖的方式降低了 LPS 刺激的 DC 的同种和同种抗原呈递活性,达到统计学意义。SB 也降低了 DC 的抗原呈递活性,但不显著。HDACIs 通过调节 DC 成熟来发挥其作用,并且在 LPS 处理之前用 TSA 或 ST 预处理 DC 可将 DC 成熟标志物的表达降低至未成熟树突状细胞(iDCs)的水平。此外,TSA 和 ST 降低了 LPS 刺激的成熟 DC 产生的 IL-2。我们的结果表明,HDACIs 可能通过抑制表型或功能成熟来积极调节 DC 诱导的炎症反应。