IL-27和TNF-α协同调节肺成纤维细胞表达CXCL10的细胞内信号途径研究

发布时间：2018-03-13 08:10

本文选题：气道炎症　切入点：肺成纤维细胞　出处：《重庆医科大学》2013年硕士论文　论文类型：学位论文

【摘要】：IL-27参与多种炎症反应。干扰素诱导蛋白10（CXCL10）是一种在气道炎症疾病中发挥重要作用的趋化因子。本研究中，我们探讨了在人的原代肺成纤维细胞（HPF）中，IL-27是否调节CXCL10的合成。IL-27或联合其他细胞因子刺激HPF，应用定量PCR和ELISA检测CXCL10的合成，应用放线菌素D检测mRNA的稳定性，应用抑制剂检测相关信号通路，Western blot加以验证。研究表明，IL-27协同TNF-α在mRNA和蛋白水平上调CXCL10的产生。这种增加CXCL10的产生主要是通过IL-27和TNF-α增强CXCL10mRNA稳定性来实现的，并且p38MAPK途径和PI3K-Akt途径的激活在此协同调节作用中起主要作用，NF-kB途径也部分参与这一过程。有趣的是，IL-27可以促进p38MAPK和Akt途径基础水平的磷酸化，，并增强TNF-α介导的上述途径的活化程度。此外，CXCL10mRNA水平稳定性的增强是依赖p38MAPK途径实现的。最终，临床研究显示哮喘、COPD和肺结核患者的支气管灌洗液中可以检测到IL-27，而且IL-27增加的水平与COPD、肺结核患者CXCL10水平增加相关。我们的研究结果表明，IL-27通过协同TNF-α刺激HLF产生CXCL10来增强气道的炎症反应。
[Abstract]:IL-27 is involved in many inflammatory reactions. The interferon inducible protein 10 (CXCL10) is a kind of play an important role in inflammatory airway disease in chemotactic factor. In this study, we investigate the fibroblasts in human primary lung (HPF),.IL-27 IL-27 CXCL10 synthesis is regulated or combined with other cytokines HPF, PCR and ELISA synthesis by quantitative detection of CXCL10, application of actinomycin D stability mRNA detection, application of detection of inhibitors of signaling pathways, Western blot is verified. The results show that IL-27 synergistically TNF- alpha in mRNA and protein levels are up-regulated CXCL10. This increased the production of CXCL10 is mainly realized by IL-27 and TNF- enhances the stability of CXCL10mRNA, and the activation of p38MAPK pathway and PI3K-Akt pathway plays a major role in the regulation of coordination, part of the NF-kB pathway is also involved in this process. Interestingly, IL-27 can promote The basic way into levels of p38MAPK and Akt phosphorylation, and enhance the degree of the activation pathway of TNF- alpha mediated. In addition, the enhancement of CXCL10mRNA level stability is dependent on p38MAPK pathway. Finally, clinical studies have shown that asthma, bronchial lavage and COPD of patients with pulmonary tuberculosis was detected in IL-27 and IL-27 increased with the level of COPD, CXCL10 levels in patients with pulmonary tuberculosis increased. Our results show that IL-27 through collaborative TNF- stimulates HLF CXCL10 to produce enhanced inflammation in the airway.

【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R563

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