Department of Neuroscience, Dental Research Institute, and Brain Korea 21, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Immunopharmacol Immunotoxicol. 2012 Dec;34(6):912-8. doi: 10.3109/08923973.2012.671332. Epub 2012 May 3.
Recent studies show that necrotic neuronal cells (NNC) activate microglia, thereby leading to neuronal cell death. This suggests that chemicals that inhibit microglia activation may be used as neuroprotective drugs. In this context, we screened a chemical library for inhibitors of microglia activation. Using a screening system based on a nitrite assay, we isolated two chemicals that inhibit nitric oxide (NO) release from activated microglia: triamcinolone acetonide (TA) and amcinonide. The half-maximal inhibitory concentrations (IC50) of TA and amcinonide for NO release inhibition were 1.78 nM and 3.38 nM, respectively. These chemicals also inhibited NNC-induced expression of the proinflammatory genes iNOS, TNF-α, and IL-1β in glial cells. A study based on a luciferase assay revealed that TA attenuated NNC-induced microglia activation by blocking the NF-κB signaling pathway. In addition, TA protected cortical neurons in coculture with microglia from LPS/IFN-γ-induced neuronal cell death. In conclusion, TA may inhibit microglia activation and may protect neuronal cells from death induced by microglial activation.
最近的研究表明，坏死的神经元细胞（NNC）会激活小胶质细胞，从而导致神经元细胞死亡。这表明抑制小胶质细胞激活的化学物质可以用作神经保护药物。在这种情况下，我们筛选了一个化学文库，以寻找小胶质细胞激活抑制剂。我们使用基于亚硝酸盐测定的筛选系统，分离出两种抑制激活的小胶质细胞释放一氧化氮（NO）的化学物质：曲安西龙丙酮（TA）和安西奈德。TA 和 amcinonide 抑制 NO 释放的半最大抑制浓度（IC50）分别为 1.78 nM 和 3.38 nM。这些化学物质还抑制了 NNC 诱导的神经胶质细胞中促炎基因 iNOS、TNF-α 和 IL-1β 的表达。基于荧光素酶测定的研究表明，TA 通过阻断 NF-κB 信号通路来减弱 NNC 诱导的小胶质细胞激活。此外，TA 还保护共培养的皮质神经元免受 LPS/IFN-γ 诱导的神经元细胞死亡。总之，TA 可能抑制小胶质细胞激活，并可能保护神经元细胞免受小胶质细胞激活引起的死亡。
