{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:19:12Z","timestamp":1780413552565,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Environmental pollution, especially particulate matter in the air, is a serious threat to human health. Long\u2010term inhalation of particulate matter with a diameter\u2009&lt;\u20092.5\u00a0\u03bcm (PM2.5) induced irreversible respiratory and lung injury. However, it is not clear whether temporary exposure to massive PM2.5 would result in epithelial damage and lung injury. More importantly, it is urgent to clarify the mechanisms of PM2.5 cytotoxicity and develop a defensive and therapeutic approach. In this study, we demonstrated that temporary exposure with PM2.5 induced lung epithelial cell apoptosis via promoting cytokines expression and inflammatory factors secretion. The cytotoxicity of PM2.5 could be alleviated by tussilagone (TSL), which is a natural compound isolated from the flower buds of Tussilago farfara. The mechanism study indicated that PM2.5 promoted the protein level of Hif\u20101\u03b1 by reducing its degradation mediated by PHD2 binding, which furtherly activated NF\u2010\u03baB signaling and inflammatory response. Meanwhile, TSL administration facilitated the interaction of the Hif\u20101\u03b1\/PHD2 complex and restored the Hif\u20101\u03b1 protein level increased by PM2.5. When PHD2 was inhibited in epithelial cells, the protective function of TSL on PM2.5 cytotoxicity was attenuated and the expression of cytokines was retrieved. Expectedly, the in vivo study also suggested that temporary PM2.5 exposure led to acute lung injury. TSL treatment could effectively relieve the damage and decrease the expression of inflammatory cytokines by repressing Hif\u20101\u03b1 level and NF\u2010\u03baB activation. Our findings provide a new therapeutic strategy for air pollution\u2010related respiratory diseases, and TSL would be a potential preventive medicine for PM2.5 cytotoxicity.<\/jats:p>","DOI":"10.1002\/tox.23476","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T11:20:37Z","timestamp":1643887237000},"page":"1198-1210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Tussilagone protects acute lung injury from <scp>PM2<\/scp>.5 via alleviating Hif\u20101\u03b1\/<scp>NF\u2010\u03baB<\/scp>\u2010mediated inflammatory response"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3637-8246","authenticated-orcid":false,"given":"Hongwei","family":"Lin","sequence":"first","affiliation":[{"name":"Respiration Department of Tangdu Hospital, Air force Military Medical University  Xi'an 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