Abstract
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.
Highlights
Cervical cancer is the fourth most common cancer form among women [1]
The increase in TLR5 occurred in the cervical epithelium (p
toll-like receptors (TLRs) 2–9 were expressed in normal, non-irradiated, cervical specimens (S4 Fig)
Summary
Cervical cancer is the fourth most common cancer form among women [1]. While earlier stages are treated with surgery, advanced stages of cervical cancer are normally treated with radiotherapy alone or in combination with chemotherapy. The understanding on what happens in the normal tissue surrounding the tumour of the cervix upon exposure of radiation is at present lacking. Radiotherapy may cause vaginal mucosal atrophy, elastosis, fibrosis and vaginal stenosis and as a consequence dyspareunia [2, 3]. While the immune system has been studied in other irradiated tissues such as the colon [4], the lung [5] and the urinary bladder [6], the immune system of the irradiated cervicovaginal tract has not been studied.
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