Nitric oxide induces p53-mediated cell death in human nasal epithelial cells

Nitric oxide (NO) is a key signaling molecule that plays a vital role in maintaining physiological homeostasis, such as immune response and neurotransmission. However, excessive NO production during inflammation and infection can lead to cytotoxicity and tissue damage. The nasal epithelial barrier is a crucial first line of immune defense against viral infection. It also prevents inflammatory substances from infiltrating the brain via the olfactory route, a vulnerable pathway directly exposed to the environment. Notably, in COVID-19, SARS-CoV-2 initially infects nasal epithelial cells, triggering local inflammation that disrupts barrier integrity and is thought to contribute to long-term symptoms such as olfactory dysfunction. However, the effect of NO exposure under chronic inflammatory conditions on the nasal epithelial barrier remains unclear. In this study, we investigated the biological effects of sustained NO exposure on the nasal epithelium using the human nasal epithelial cell line RPMI2650. Transcriptomic analysis after NO exposure revealed significant upregulation of p53 signaling pathway related genes. Furthermore, RT-qPCR confirmed the time-dependent upregulation of the p53 target genes, which are associated with apoptosis and cell cycle arrest. These gene expression changes led to reduced cell proliferation and increased cell death. Our findings suggest that excessive NO induces nasal epithelial cell death through the p53 pathway. Furthermore, this mechanism may underlie long-term tissue damage and functional impairment under inflammatory conditions. This study provides new insights into how prolonged NO exposure compromises the nasal epithelial barrier and contributes to the chronic progression of infectious diseases and olfactory dysfunction.