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研究登革病毒(Dengue virus,DENV)感染对人单核细胞中血管内皮细胞生长因子(Vascular endothelialgrowth factor,VEGF)表达的影响,并检测分析可影响VEGF表达的天然免疫信号通路。通过Real-time PCR检测,发现不同型DENV(DENV1、DENV2、DENV3)感染THP-1细胞均可诱导VEGF mRNA表达水平呈时间依赖性增加;而DENV2感染也可上调VEGF在原代单核细胞中的表达。通过RNAi技术沉默Toll样受体3(TLR3)及接头蛋白IPS-1,发现DENV感染诱导的VEGF表达明显下调;而ERK、JNK及NF-κB等信号通路的抑制也可下调VEGF的表达水平。本研究证明,DENV感染可诱导人单核细胞中的VEGF高表达,而VEGF高表达依赖于TLR3及IPS-1信号通路的激活,提示VEGF可能是治疗登革出血热的一个靶点。
To investigate the effect of Dengue virus (DENV) infection on the expression of vascular endothelial growth factor (VEGF) in human monocytes, and to detect and analyze the natural immune signal pathways that may affect the expression of VEGF. Real-time PCR showed that the expression of VEGF mRNA in THP-1 cells induced by different types of DENV (DENV1, DENV2, DENV3) could be increased in a time-dependent manner. However, DENV2 infection could up-regulate the expression of VEGF in primary monocytes expression. The silencing of Toll-like receptor 3 (TLR3) and adapter protein IPS-1 by RNAi showed that the expression of VEGF was down-regulated by DENV infection. The inhibition of ERK, JNK and NF-κB signaling pathway also downregulated the expression of VEGF. This study demonstrated that DENV infection can induce high expression of VEGF in human monocytes, whereas high expression of VEGF relies on the activation of TLR3 and IPS-1 signaling pathways, suggesting that VEGF may be a target for the treatment of dengue hemorrhagic fever.