Moderate Dose Irradiation Induces DNA Damage and Impairments of Barrier and Host Defense in Nasal Epithelial Cells in vitro.
Moderate Dose Irradiation Induces DNA Damage and Impairments of Barrier and Host Defense in Nasal Epithelial Cells in vitro.
复制标题
中等剂量辐射体外诱导鼻上皮细胞 DNA 损伤以及屏障和宿主防御损伤
DOI：
10.2147/jir.s369385
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发表时间：
2022
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
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作者：
放射治疗（RT）是头颈部癌症的主要治疗方法。然而，慢性和复发性上呼吸道感染和炎症在RT后的患者中常见，其潜在机制仍知之甚少。我们使用了一个完善的人鼻上皮细胞（hNECs）模型，该模型在气液界面（ALI）形成假复层，并将其暴露于单次或重复中等剂量γ射线（1Gy）。我们评估了DNA损伤，并评估了hNECs在RT后不同时间点的生物学特性。此外，我们探讨了宿主免疫功能的变化，在辐射hNECs与聚肌胞苷酸钠盐（poly [I：C]）和脂多糖（LPS）。IR诱导hNECs DNA双链断裂（DSB），引发DNA损伤反应。反复IR显著降低基底细胞增殖，p63/KRT 5和Ki 67表达降低，诱导纤毛脱落，抑制粘液分泌。此外，IR降低ZO-1的表达，并引起跨上皮电阻（TEER）的显着下降。此外，对病原体入侵和破坏上皮宿主防御的高反应性反应，可以观察到暴露于反复IR的hNECs。我们的研究表明，IR诱导的长期结构和功能障碍的hNECs可能有助于患者RT后发展慢性和复发性上呼吸道感染和炎症的风险增加。
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. 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). 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. 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.