Elsisi Nahed S, Darling-Reed Selina, Lee Eunsook Y, Oriaku Ebenezer T, Soliman Karam F
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahaeess, FL 32307, USA.
Neurosci Lett. 2005 Feb 28;375(2):91-6. doi: 10.1016/j.neulet.2004.10.087. Epub 2004 Dec 8.
In case of injury or disease, microglia are recruited to the site of the pathology and become activated as evidenced by morphological changes and expression of pro-inflammatory cytokines. Evidence suggests that microglia proliferate by cell division to create gliosis at the site of pathological conditions such as the amyloid plaques in Alzheimer's disease and the substantia nigra of Parkinson's disease patients. The hyperactivation of microglia contributes to neurotoxicity. In the present study we tested the hypothesis that anti-inflammatory compounds modulate the progression of cell cycle and induce apoptosis of the activated cells. We investigated the effects of ibuprofen (non-steroidal anti-inflammatory drug) and apigenin (a flavonoid with anti-inflammatory and anti-proliferative properties) on the cell cycle of the murine microglial cell line BV-2. The findings indicate that apigenin-induced cell cycle arrest preferentially in the G2/M phase and ibuprofen caused S phase arrest. The binding of annexin V-FITC to the membranes of cells which indicates the apoptotic process were examined, whereas the DNA was stained with propidium iodide. Both apigenin and ibuprofen induced apoptosis significantly in early and late stages. The induction of apoptosis by ibuprofen and apigenin was confirmed using TUNEL assay, revealing that 25 microM apigenin and 250 microM ibuprofen significantly increased apoptosis in BV-2 cells. The results from the present study suggest that anti-inflammatory compounds might inhibit microglial proliferation by modulating the cell cycle progression and apoptosis.
在发生损伤或疾病时，小胶质细胞会被募集到病变部位并被激活，形态变化和促炎细胞因子的表达即为证据。有证据表明，小胶质细胞通过细胞分裂进行增殖，从而在诸如阿尔茨海默病中的淀粉样斑块以及帕金森病患者的黑质等病理状况部位形成胶质增生。小胶质细胞的过度激活会导致神经毒性。在本研究中，我们检验了以下假设：抗炎化合物可调节细胞周期进程并诱导活化细胞凋亡。我们研究了布洛芬（一种非甾体抗炎药）和芹菜素（一种具有抗炎和抗增殖特性的黄酮类化合物）对小鼠小胶质细胞系BV-2细胞周期的影响。研究结果表明，芹菜素诱导细胞周期优先停滞在G2/M期，而布洛芬导致S期停滞。检测了膜联蛋白V-FITC与细胞表面的结合情况，这表明了凋亡过程，同时用碘化丙啶对DNA进行染色。芹菜素和布洛芬在早期和晚期均显著诱导细胞凋亡。使用TUNEL检测法证实了布洛芬和芹菜素诱导细胞凋亡，结果显示25微摩尔的芹菜素和250微摩尔的布洛芬可显著增加BV-2细胞的凋亡。本研究结果表明，抗炎化合物可能通过调节细胞周期进程和凋亡来抑制小胶质细胞增殖。
