Moderate Dose Irradiation Induces DNA Damage and Impairments of Barrier and Host Defense in Nasal Epithelial Cells in vitro

Yue-Ying Yang; Jing Liu; Yi-Tong Liu; Hsiao-Hui Ong; Qian-Min Chen; Ce-Belle Chen; Mark Thong; Xinni Xu; Sui-Zi Zhou; Qian-Hui Qiu; De-Yun Wang

doi:10.2147/JIR.S369385

Moderate Dose Irradiation Induces DNA Damage and Impairments of Barrier and Host Defense in Nasal Epithelial Cells in vitro

J Inflamm Res. 2022 Jun 25:15:3661-3675. doi: 10.2147/JIR.S369385. eCollection 2022.

Authors

Yue-Ying Yang^#^{1

2}, Jing Liu^#², Yi-Tong Liu^{3

4}, Hsiao-Hui Ong², Qian-Min Chen^{2

4}, Ce-Belle Chen⁵, Mark Thong⁶, Xinni Xu⁶, Sui-Zi Zhou^{3

4}, Qian-Hui Qiu^{3

4}, De-Yun Wang²

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
² Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
³ Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
⁴ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People's Republic of China.
⁵ Centre for Ion Beam Applications, Department of Physics, National University of Singapore, Singapore.
⁶ Department of Otolaryngology-Head and Neck Surgery, National University Hospital, National University Health System, Singapore.

^# Contributed equally.

Abstract

Purpose: Radiotherapy (RT) is the mainstay treatment for head and neck cancers. However, chronic and recurrent upper respiratory tract infections and inflammation have been commonly reported in patients post-RT. The underlying mechanisms remain poorly understood.

Method and materials: We used a well-established model of human nasal epithelial cells (hNECs) that forms a pseudostratified layer in the air-liquid interface (ALI) and exposed it to single or repeated moderate dose γ-irradiation (1Gy). We assessed the DNA damage and evaluated the biological properties of hNECs at different time points post-RT. Further, we explored the host immunity alterations in irradiated hNECs with polyinosinic-polycytidylic acid sodium salt (poly [I:C]) and lipopolysaccharides (LPS).

Results: IR induced DNA double strand breaks (DSBs) and triggered DNA damage response in hNECs. Repeated IR significantly reduced basal cell proliferation with low expression of p63/KRT5 and Ki67, induced cilia loss and inhibited mucus secretion. In addition, IR decreased ZO-1 expression and caused a significant decline in the transepithelial electrical resistance (TEER). Moreover, hyperreactive response against pathogen invasion and disrupted epithelial host defense can be observed in hNECs exposed to repeated IR.

Conclusion: Our study suggests that IR induced prolonged structural and functional impairments of hNECs may contribute to patients post-RT with increased risk of developing chronic and recurrent upper respiratory tract infection and inflammation.

Keywords: DNA double strand breaks; epithelial barrier; host defense; human nasal epithelial cells; irradiation.

Grants and funding

This research was funded by the National Medical Research Council, Singapore No. NMRC/CIRG/1458/2016 (to De-Yun Wang), and National Natural Science Foundation of China No. 81873690 & No. 82171104 (to Qian-Hui Qiu).