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金雀异黄素通过诱导巨噬细胞中 p38MAPK 的激活诱导形态变化和 G2/M 细胞周期停滞。

Genistein induces morphology change and G2/M cell cycle arrest by inducing p38 MAPK activation in macrophages.

机构信息

Medical College of Yangzhou University, Huaihai Road 11, 225001, Yangzhou, China; Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany.

Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany.

出版信息

Int Immunopharmacol. 2014 Jan;18(1):142-50. doi: 10.1016/j.intimp.2013.11.016. Epub 2013 Nov 26.

DOI:10.1016/j.intimp.2013.11.016
PMID:24290959
Abstract

Genistein is a well known natural compound which is present in soy foods and exerts many beneficial functions such as anticancer, anti-inflammatory and antioxidant. However, until now little is known about the effects of genistein on the function of macrophages. The murine macrophage cell line RAW264.7 was used as target cell line. The results show that at concentrations of 50-100μM, genistein reduced cell viability to 70%-80% (after 24h) and 50%-60% (after 48h), which was due to G2/M phase cell cycle arrest. Treatment of the macrophages with genistein for 24 or 48h also led to significant morphological changes, such as elongation of the cells and development of long pseudopodia-like protrusions. By staining the F-actin cytoskeleton, we observed accumulation of actin-filaments at the edges of the cells. The morphology change and G2/M phase arrest after genistein treatment is due to the activation of the phosphorylation of MAP kinase p38. The morphology change and cell cycle arrest can be significantly reverted when treatment is combined with p38 inhibitor SB203580. Moreover, after treatment of the macrophages with genistein for 24 and 48h, the phagocytotic efficiency for Candida albicans was decreased in a time- and dose-dependent manner which correlates to the morphology change. The production of cytokines (TNF-α) stimulated by C. albicans was strongly inhibited by genistein. In conclusion, genistein showed a strong immune modulatory effect on the macrophages.

摘要

染料木黄酮是一种存在于大豆食品中的天然化合物,具有许多有益的功能,如抗癌、抗炎和抗氧化作用。然而,直到现在,人们对染料木黄酮对巨噬细胞功能的影响知之甚少。本研究以小鼠巨噬细胞系 RAW264.7 为靶细胞系。结果表明,在 50-100μM 浓度下,染料木黄酮将细胞活力降低至 70%-80%(24h 后)和 50%-60%(48h 后),这是由于 G2/M 期细胞周期停滞所致。用染料木黄酮处理巨噬细胞 24 或 48h 也会导致明显的形态变化,如细胞伸长和长伪足样突起的发育。通过对 F-肌动蛋白细胞骨架进行染色,我们观察到细胞边缘处肌动蛋白丝的积累。染料木黄酮处理后的形态变化和 G2/M 期阻滞是由于 MAP 激酶 p38 的磷酸化激活所致。当与 p38 抑制剂 SB203580 联合治疗时,形态变化和细胞周期阻滞可以显著逆转。此外,用染料木黄酮处理巨噬细胞 24 和 48h 后,白色念珠菌的吞噬效率呈时间和剂量依赖性下降,与形态变化相关。染料木黄酮强烈抑制白色念珠菌刺激产生的细胞因子(TNF-α)。总之,染料木黄酮对巨噬细胞表现出强烈的免疫调节作用。

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