Radiation induces changes in toll-like receptors of the uterine cervix of the rat

Radiotherapy is an important therapeutic approach against cervical cancer but associated with adverse effects including vaginal fibrosis and dyspareunia. We here assessed the immunological and oxidative responses to cervical irradiation in an animal model for radiation-induced cervicitis. Rats were sedated and either exposed to 20 Gy of ionising radiation given by a linear accelerator or only sedated (controls) and euthanized 1–14 days later. The expressions of toll-like receptors (TLRs) and coupled intracellular pathways in the cervix were assessed with immunohistofluorescence and western blot. Expression of cytokines were analysed with the Bio-Plex Suspension Array System (Bio-Rad). We showed that TLRs 2–9 were expressed in the rat cervix and cervical irradiation induced up-regulation of TLR5, TRIF and NF-κB. In the irradiated cervical epithelium, TLR5 and TRIF were increased in concert with an up-regulation of oxidative stress (8-OHdG) and antioxidant enzymes (SOD-1 and catalase). G-CSF, M-CSF, IL-10, IL- 17A, IL-18 and RANTES expressions in the cervix decreased two weeks after cervical irradiation. In conclusion, the rat uterine cervix expresses the TLRs 2–9. Cervical irradiation induces immunological changes and oxidative stress, which could have importance in the development of adverse effects to radiotherapy.

放疗是针对宫颈癌的重要治疗手段，但与其相关的副作用包括阴道纤维化和性交疼痛。本研究旨在评估动物模型中因放射诱导的宫颈炎而对宫颈照射的免疫学和氧化应激反应。实验中，将大鼠进行镇静处理，并分别接受由直线加速器提供的20 Gy离子辐射（实验组）或仅进行镇静处理（对照组），并在1至14天后进行安乐死。通过免疫组织化学和蛋白质印迹技术评估宫颈中 Toll 样受体（TLRs）及其偶联的细胞内信号通路。使用 Bio-Plex 悬浮阵列系统（Bio-Rad）分析细胞因子的表达。结果显示，大鼠宫颈中表达 TLRs 2-9，宫颈照射诱导了 TLR5、TRIF 和 NF-κB 的上调。在照射的宫颈上皮中，TLR5 和 TRIF 的表达与氧化应激（8-OHdG）和抗氧化酶（SOD-1 和过氧化氢酶）的上调同步增加。在宫颈照射两周后，宫颈中 G-CSF、M-CSF、IL-10、IL-17A、IL-18 和 RANTES 的表达均有所下降。综上所述，大鼠子宫颈表达 TLRs 2-9。宫颈照射可诱导免疫学变化和氧化应激，这些变化可能对放疗不良反应的发生具有重要意义。