{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:46Z","timestamp":1787022166556,"version":"build-2736575974"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K08564"],"award-info":[{"award-number":["22K08564"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K11579"],"award-info":[{"award-number":["24K11579"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K16549"],"award-info":[{"award-number":["21K16549"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Quercetin is known for its ability to inhibit mast cell degranulation and reduce the release of inflammatory mediators. However, it has also been reported to sensitize mast cells, potentially leading to hyperresponsiveness. This necessitates careful optimization of its use in the treatment of chronic inflammatory diseases. To fully harness quercetin\u2019s therapeutic potential, this study investigated the effects of quercetin on rat basophilic leukemia (RBL-2H3) cells responsiveness over varying durations of exposure. We employed comprehensive transcriptome analysis and subsequent functional validation of key signaling pathways. Our findings revealed that quercetin initially reduced cell activity with short-term treatment. However, with prolonged exposure, quercetin transiently enhanced both IgE cross-linkage-mediated and non-IgE-mediated responses. Specifically, prolonged quercetin treatment downregulated IgE-mediated degranulation and Fc\u03b5RI expression, while potentially sensitizing RBL-2H3 cells to other non-IgE secretagogues through enhanced PKC activity. Given quercetin\u2019s multifaceted effects on intracellular signaling pathways, it is crucial to further investigate its efficacy and potential risk of adverse effects. Future studies should focus on a deeper understanding of these mechanisms to optimize quercetin\u2019s therapeutic applications while mitigating any possible negative outcomes.<\/jats:p>","DOI":"10.1371\/journal.pone.0319103","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T13:51:13Z","timestamp":1740405073000},"page":"e0319103","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Time-sensitive effects of quercetin on rat basophilic leukemia (RBL-2H3) cell responsiveness and intracellular 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