Intravenous anesthetic propofol suppresses prostaglandin E2 production in murine dendritic cells
Intravenous anesthetic propofol suppresses prostaglandin E2 production in murine dendritic cells
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DOI：
10.3109/1547691x.2011.620036
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发表时间：
2011-10-01
影响因子：
3.3
通讯作者：
Shingu, Koh
中科院分区：
文献类型：
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作者：
Inada, Takefumi;Kubo, Kozue;Shingu, Koh
异丙酚是一种静脉麻醉药，广泛用于麻醉和镇静。树突状细胞 (DC) 是连接先天免疫和适应性免疫的关键免疫细胞之一，其中 DC 在先天免疫反应过程中处理抗原，将其呈递给初始 T 细胞，从而建立适应性免疫。前列腺素（PG）-E-2可能由DC分泌到微环境中，显着影响DC的表型和功能，从而决定适应性免疫的命运。由于异丙酚抑制小鼠巨噬细胞中PGE(2)的产生，本研究的主要目的是确定异丙酚是否也抑制DC中PGE(2)的产生。假设这种抑制得到了积极的发现，我们测试了这是否也会导致白介素 (IL)-12 和 IL-10 产生以及 DC 表面标志物表达的改变，这两者都可以通过 PGE(2) 调节。在骨髓来源的 DC 中，丙泊酚显着抑制脂多糖刺激后 PGE(2) 的产生。环加氧酶（COX）蛋白表达和花生四烯酸释放不受影响，而异丙酚显着抑制COX酶活性。异丙酚诱导的 COX 抑制不会导致半胱氨酰白三烯和白三烯-B-4 的产生增加。使用丙泊酚以及选择性 COX-2 抑制剂 NS-398 进行内源性 COX 抑制，不会影响 DC 产生 IL-12 和 IL-10。丙泊酚和 NS-398 均未改变 DC 表面 I-A(b) 和 CD40 的表达，而 CD86 的表达略有增加； CD80 的表达不受丙泊酚影响，但 NS-398 略有增加。最后，异丙酚或 NS-398 的内源性 COX 抑制不会显着影响 DC 诱导同种异体 T 细胞增殖的能力。结论是，静脉麻醉异丙酚抑制 DC 中的 COX 酶活性，对 IL-12/IL-10 产生和同种异体 T 细胞增殖没有影响，而对表面分子表达的影响最小。
Propofol is an intravenous anesthetic that is widely used for anesthesia and sedation. Dendritic cells (DC) are one of the crucial immune cells that bridge innate and adaptive immunity, in which DC process antigens during innate immune responses to present them to naive T-cells, leading to an establishment of adaptive immunity. Prostaglandin (PG)-E-2 may be secreted by DC into the microenvironment, considerably influencing DC phenotype and function, and thus determining the fate of adaptive immunity. Since propofol suppresses PGE(2) production in murine macrophages, the primary purpose of the present study was to determine whether propofol also suppresses PGE(2) production in DC. Assuming a positive finding of such suppression, we tested whether this also leads to alterations of interleukin (IL)-12 and IL-10 production and DC surface marker expression, both of which can be modulated by PGE(2). In bone marrow-derived DC, propofol significantly suppressed the PGE(2) production after lipopolysaccharide stimulation. Cyclo-oxygenase (COX) protein expression and arachidonic acid release were unaffected, while COX enzyme activity was significantly inhibited by propofol. The propofol-induced COX inhibition did not lead to the increased production of cysteinyl leukotrienes and leukotriene-B-4. Endogenous COX inhibition with propofol, as well as with the selective COX-2 inhibitor, NS-398, did not affect IL-12 and IL-10 production from DC. The surface expression of I-A(b) and CD40 on DC was not changed, while that of CD86 slightly increased, with both propofol and NS-398; expression of CD80 was not affected with propofol, but increased slightly with NS-398. Finally, endogenous COX inhibition with either propofol or NS-398 did not significantly affect the ability of DC to induce allogeneic T-cell proliferation. It is concluded that the intravenous anesthetic propofol suppresses COX enzyme activity in DC, with no consequences with respect to IL-12/IL-10 production and allogeneic T-cell proliferation, while minimal consequences were observed in surface molecule expression.