Abstract
Nitric oxide (NO) is a key signaling molecule that plays a vital role in maintaining homeostasis of physiological processes such as immune responses and neurotransmission. However, excessive NO production during inflammatory responses to infection can lead to cytotoxicity and tissue damage. The nasal epithelial barrier is a crucial first line of immunological defense against viral infections, and it is likely exposed to excessive NO levels during chronic inflammation. Therefore, clarifying the effects of NO on this barrier is thus critical. In this study, we investigated the biological effects of sustained NO exposure on RPMI2650 human nasal epithelial cells. Post-NO exposure transcriptomic analyses revealed significant upregulation of genes involved in the p53 signaling pathway. RT-qPCR analyses confirmed the temporal upregulation of p53 target genes associated with apoptosis and cell cycle regulation. These gene expression changes downregulated cell proliferation and induced cell death. Our findings suggest that excessive NO exposure induces nasal epithelial cell death via the p53 pathway, which over the long term can result in tissue damage and dysfunction under inflammatory conditions. These results provide new insights into how prolonged NO exposure affects the nasal epithelial cells and may contribute to the progression of chronic infectious diseases.
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Data availability
RNA sequencing data were deposited in the DDBJ (https://ddbj.nig.ac.jp/search/en) under accession number PRJDB35845.
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Acknowledgements
We thank Kotoe Sueyoshi and Eriko Nishimura for technical assistance.
Funding
This research was funded by grants-in-aid for Challenging Exploratory Research (22K19380 to T.U.) and Scientific Research (A) (24H00678 to T.U.) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. Funding was also provided by the Smoking Research Foundation (to T.U.) and the JSPS Program for Forming Japan’s Peak Research Universities (J-PEAKS) (JPJS00420230010).
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T.U. conceived and designed the study. S.K. (Shizuki Kamiuezono) acquired and initially analyzed the data. S.K. (Shizuki Kamiuezono), S.K. (Sho Kubota), and T.T. conducted further analyses. S.K. (Shizuki Kamiuezono) drafted the manuscript. S.K. (Sho Kubota) and N.T. substantively revised the manuscript. All authors approved the submitted version.
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Kamiuezono, S., Kubota, S., Tsuchida, T. et al. Nitric oxide induces p53-mediated cell death in human nasal epithelial cells. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40908-6
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DOI: https://doi.org/10.1038/s41598-026-40908-6
