IL-1 maintains the redox balance by regulating glutaredoxin 1 expression during oral carcinogenesis
IL-1 maintains the redox balance by regulating glutaredoxin 1 expression during oral carcinogenesis
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IL-1β 通过调节口腔癌发生过程中谷氧还蛋白 1 的表达来维持氧化还原平衡
DOI：
10.1111/jop.12502
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发表时间：
2017-05-01
影响因子：
3.3
通讯作者：
Wu, Tong
中科院分区：
文献类型：
--
作者：
Chen, Xijuan;Lv, Qianshu;Wu, Tong
白介素1β(IL-1β)是一种与癌症炎症相关的多效性细胞因子，已有报道在多种癌症中上调。我们前期的研究发现，IL-1是口腔癌变过程中的关键节点基因之一，谷氧还蛋白1(Grx1)是肿瘤微环境中IL-1的下游基因之一。Grx1是一种普遍存在的氧化还原酶，在清除活性氧自由基(ROS)和维持细胞内氧化还原平衡方面是必需的。方法从4NQO诱导的大鼠口腔癌变模型和人口腔黏膜获取不同癌变阶段的粘膜标本，用免疫组织化学方法检测Grx1的表达。分别检测IL-1ra或NAC处理前后口腔鳞癌细胞CAL27细胞内ROS水平和Grx1mRNA水平。Leti-si-IL-1和Leti-si-NC CAL27细胞经IL-1刺激后检测到ROS水平。Transwell法检测IL-1刺激前后CAL27细胞的侵袭和迁移能力。结果Grx1表达与体内恶性转化过程有关。外源性IL-1上调CAL27细胞内ROS水平和Grx1表达，IL-1ra可拮抗外源性IL-1上调细胞内ROS水平和Grx1表达。外源性IL-1诱导的细胞内ROS积聚是Grx1上调的原因之一。结论IL-1通过调节Grx1的表达，在口腔鳞癌发生发展过程中调控氧化还原平衡，参与口腔鳞癌细胞的侵袭和迁移。
BackgroundInterleukin-1 beta (IL-1) is a pleiotropic cancer-inflammation-linked cytokine which has been reported upregulated in many cancers. In our previous study, IL-1 was found to be one of the key node genes during oral malignant transformation, and glutaredoxin 1 (Grx1) was identified as one of the downstream genes of IL-1 in tumor microenvironment. Grx1 is ubiquitous oxidoreductase which is necessary for scavenging reactive oxygen species (ROS) and the intracellular redox balance maintenance.MethodsTissues from different stages of mucosal malignant transformation were obtained from 4NQO-induced rat oral carcinogenesis model and human mucosa for Grx1 expression detection by immunohistochemical staining. The intracellular ROS levels and Grx1 mRNA level of oral squamous carcinoma cell CAL27 were detected after IL-1 treatment with or without pretreatment of IL-1Ra or NAC, respectively. The ROS levels were detected in Leti-si-IL-1 and Leti-si-NC CAL27 cells after IL-1 stimulation. The invasion and migration abilities of CAL27 cells were tested by transwell assay after IL-1 stimulation with or without pretreatment of IL-1Ra.ResultsGrx1 expression was associated with the malignant transformation process in vivo. Exogenous IL-1 upregulated the intracellular ROS level and the expression of Grx1 in CAL27 cells, which could be counteracted by IL-1Ra. The intracellular ROS accumulation induced by exogenous IL-1 was responsible for the Grx1 upregulation. Endogenous IL-1 acted as a switch in regulating the ROS level by modulating Grx1 expression, which was involved in the invasion and migration of OSCC cells.ConclusionsIL-1 finely orchestrated the redox balance during carcinogenesis by modulating Grx1 expression.