HPV11E7 inhibits IMQ-induced chemokine and colony-stimulating factor production in keratinocytes
HPV11E7 inhibits IMQ-induced chemokine and colony-stimulating factor production in keratinocytes
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HPV11E7 抑制角质形成细胞中 IMQ 诱导的趋化因子和集落刺激因子的产生
DOI：
10.1016/j.gene.2020.145003
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发表时间：
2020-11-15
期刊：
影响因子：
3.5
通讯作者：
Cheng，Hao
中科院分区：
文献类型：
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作者：
Zheng，Huimin;Zou，Ziqi;Cheng，Hao
咪喹莫特(Imq)被批准为治疗由人类乳头瘤病毒(HPV)感染引起的生殖器疣的一线药物。然而，复发率很高。HPV E7蛋白在HPV免疫逃逸中起重要作用。然而，HPV11E7蛋白在ImQ治疗期间生殖器尖锐湿疣复发中的作用尚不清楚。在这里，我们发现ImQ处理后NHEK细胞的表达谱发生了明显的变化，大量编码细胞因子的基因以及参与细胞因子介导的信号通路和细胞代谢信号通路的基因上调或下调。HPV11E7过表达可抑制ImQ诱导的NHEK细胞产生多种趋化因子和集落刺激因子。此外，我们还发现HPV11E7可以破坏丝裂原活化蛋白激酶(MAPK)信号通路的激活。因此，我们的结果提示，HPV11E7通过抑制MAPK信号通路减少趋化因子、集落刺激因子和其他细胞因子的产生，从而抑制ImQ的治疗效果，促进疾病的复发，如尖锐湿疣。
Imiquimod (IMQ) is approved as a first-line treatment for genital warts caused by human papillomavirus (HPV) infection. However, the recurrence rate is very high. HPV E7 protein plays a critical role in HPV immune escape. However, the role of HPV11 E7 protein in genital warts recurrence during IMQ treatment is not clear. Here, we found that the expression profile of NHEK cells was obviously changed after IMQ treatment, and a large number of genes encoding cytokines and genes involved in cytokine-mediated signaling pathways and cellular metabolic signaling pathways were up- or downregulated. HPV11E7 overexpression inhibited the IMQ-induced production of of multiple chemokines and colony-stimulating factors in NHEK cells. Furthermore, we found that HPV11E7 could impair the activation of mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, our results suggested that HPV11 E7 diminishes the production of chemokines, colony-stimulating factors and other cytokines via inhibition of the MAPK signaling pathway, which suppresses the therapeutic effect of IMQ and promotes the recurrence of diseases, such as condyloma acuminatum.