结核菌脂阿拉伯甘露糖通过Notch1介导结核免疫逃避的实验研究  被引量:2

Experimental study on tuberculosis immune escape medicated by tuberculosis lipid arabia mannose via Notch 1

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作  者:李良[1] LI Licng(Emergency Center,Taizhou Hospital in Zhejiang Province,Linhai 317000,China)

机构地区:[1]浙江省台州医院急救中心,浙江临海317000

出  处:《中国现代医生》2018年第11期22-25,29,共5页China Modern Doctor

基  金:浙江省医药卫生科技计划项目(2017KY706)

摘  要:目的探讨Notch1信号通路在结核菌脂阿拉伯甘露糖(LAM)诱导的结核免疫逃避中的作用。方法使用腹腔注射LAM,以及LAM+Notch通路抑制剂(GSI),收获小鼠腹腔巨噬细胞,RT-PCR法进行Notch1 mRNA转录水平的研究,Western Blot法对Notch1受体表达水平进行鉴定,ELISA法检测细胞因子IL-1β、INF-γ、IL-12的分泌水平。结果经LAM刺激后的小鼠腹腔巨噬细胞Notch1受体的转录水平与表达水平均升高。IL-1β、IL-12、炎症介质分泌水平显著下降,GSI干预能减弱IL-1β、IL-12的下降趋势。而INF-γ分泌水平不受LAM以及GSI干预的影响。结论 Notch1信号通路在LAM诱导的结核分枝杆菌免疫逃避中有着重要的作用,而基于Notch信号通路的治疗方法在不久的将来可能为潜伏结核感染(LTBI)患者或者难治性结核病患者提供新的治疗思路。Objective To investigate the role of Notch1 signaling pathway in tuberculosis immune escape induced by tuberculosis lipid Arabia mannose(LAM). Methods Intraperitoneal injection of LAM was carried out, and LAM+Notch pathway inhibitor(GSI)was used. Mouse peritoneal macrophages were harvested. RT-PCR method was used for the study on Notch1 mRNA transcription levels, Western Blot method was used for the identification of Notch1 receptor expression levels, and the secretory levels of IL-1β, INF-γ and IL-12 were detected by ELISA method. Results The transcription levels and expression levels of Notch1 receptors in mouse peritoneal macrophages stimulated by LAM were all increased. IL-1β, IL-12, and secretory levels of inflammatory mediators were decreased significantly. GSI intervention could reduce the decreasing trend of IL-1β and IL-12, and the secretory level of INF-γ was not affected by LAM and GSI intervention. Conclusion Notch1 signaling pathway plays an important role in LAM-induced immune escape of mycobacterium tuberculosis. However, the treatment method based on the Notch signaling pathway may provide a new therapeutic option for patients with latent tuberculosis infection(LTBI)or refractory tuberculosis in the near future.

关 键 词:结核 阿拉伯甘露糖 NOTCH1 免疫逃避 

分 类 号:R446[医药卫生—诊断学]

 

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