| 伊马替尼抑制脂多糖诱导的巨噬细胞炎症表型 |
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| 引用本文： | 王乐旬,吴惠娟,张盛昔,杨潇,郭姣. 伊马替尼抑制脂多糖诱导的巨噬细胞炎症表型[J]. 中山大学学报(医学科学版), 2019, 40(5): 689 |
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| 作者姓名： | 王乐旬 吴惠娟 张盛昔 杨潇 郭姣 |
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| 作者单位： | 1.广东省代谢病中西医结合研究中心//广东省代谢性疾病中医药防治重点实验室//粤港澳联合代谢病重点实验室//广东药科大学中医药研究院，广东广州510006；2.华南理工大学附属第二医院//广州市第一人民医院检验科，广东广州510180 |
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| 基金项目： | 广东省自然科学基金博士启动纵向协同项目（2018A030310403）；广东省自然科学基金（2018A0303130168）；广东省医学科研基金（A2018068）；广州市卫生健康科技项目（西医类-一般引导项目，20191A011013） |
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| 摘 要： | 【目的】探讨伊马替尼（Ima）在体外对脂多糖（LPS）诱导的RAW264.7巨噬细胞炎症表型的影响。【方法】RAW264.7细胞在LPS（0.1μg/mL）或/和Ima（1μmol/L，5μmol/L）处理后，通过Q-PCR方法检测细胞因子IL-1β、IL-10、CCL2、iNOS、TNF-α和Arg1的mRNA表达变化；采用Western Blot检测iNOS蛋白表达变化以及NF-κB和MAPK信号通路活化情况；利用ELISA法检测细胞上清IL-1β、CCL2、IL-10和TNFα的蛋白表达情况。【结果】与对照组相比较，LPS刺激8h后，RAW264.7细胞内的炎症指标IL-1β、CCL2、iNOS和TNF-α的mRNA水平显著升高（P<0.001）以及抗炎指标IL-10的mRNA水平也明显升高（P<0.001）；LPS刺激24h后，细胞上清中IL-1β、IL-10、CCL2和TNF-α的蛋白水平显著上升（P<0.001），细胞内iNOS蛋白表达以及p65，p38，ERK和AKT的磷酸化水平显著增加。和LPS组相比，Ima提前处理后，IL-1β、CCL2、iNOS和TNF-α的mRNA及蛋白水平显著下降（P<0.01，P<0.001）而IL-10的mRNA及蛋白水平显著升高（P<0.001），这种抑制作用具有剂量依赖性。Ima的预处理抑制了LPS诱导的p65，p38，ERK和AKT磷酸化。单独用Ima处理RAW264.7细胞后，细胞的功能状态未见明显的改变。【结论】伊马替尼可抑制LPS诱导的巨噬细胞炎症表型，这种作用与抑制NF-κB和MAPK信号通路的过度激活有关。
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| 关 键 词： | 伊马替尼 巨噬细胞 炎症因子 信号通路 |
| 收稿时间： | 2019-05-13 |
Imatinib Inhibits the Inflammatory Phenotype of Macrophage Induced by Lipopolysaccharide |
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| WANG Le-xun,WU Hui-juan,ZHANG Sheng-xi,YANG Xiao,GUO Jiao. Imatinib Inhibits the Inflammatory Phenotype of Macrophage Induced by Lipopolysaccharide[J]. Journal of Sun Yatsen University(Medical Sciences), 2019, 40(5): 689 |
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| Authors: | WANG Le-xun WU Hui-juan ZHANG Sheng-xi YANG Xiao GUO Jiao |
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| Abstract: | 【Objective】To investigate the effect of Imatinib（Ima）on the inflammatory phenotype of RAW264.7 macrophages induced by lipopolysaccharide （LPS）. 【Methods】 RAW264.7 cells were treated by LPS （0.1 μg/mL） and/or Ima（1 μmol/L，5 μmol/L）. The mRNA levels of IL- 1β，IL- 10，CCL2，iNOS，TNF- α and Arg1 in RAW264.7 cells were tested by Q-PCR. The iNOS protein level and the activation of NF- κB and MAPK signal pathways were detected by Western Blot. The protein levels of IL- 1 β ，CCL2 ，IL-10 and TNF- α in cell supernatant were detected by ELISA.【Results】Compared with the normal control group，the mRNA levels of IL- 1β，CCL2，iNOS，TNF- α and IL- 10 were significantly increased in RAW264.7 cells treated with LPS for 8 h（P<0.001）. In addition，the cell supernatant protein levels of IL- 1β，IL- 10，CCL2 as well as TNFα and the iNOS protein level were significantly increased in RAW264.7 cells stimulated by LPS for 24 h（P<0.001）. Moreover ，the phosphorylation levels of p65 ，p38 ，ERK and AKT were enhanced in RAW264.7 cells after treatment with LPS for 24 h. Compared with LPS group，pretreatment with Ima decreased the mRNA and protein levels of IL-1β，CCL2，iNOS and TNF- α（P<0.01，P<0.001），but increased the mRNA and protein level of IL-10（P<0.001）. And this effect of Ima was dose-dependent. The phosphorylation levels of p65，p38， ERK and AKT were decreased in LPS+Ima group compared with that in LPS group. The functional status of RAW264.7 cells did not change significantly after treatment with Ima alone.【Conclusions】The effect of Imatinib to inhibit the inflammatory phenotype of macrophage is related to retarding the overactivation of NF-κB and MAPK signaling pathways. |
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| Keywords: | Imatinib macrophage inflammatory factors signaling pathway |
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