{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:35:11Z","timestamp":1793252111767,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018684","name":"National Health Commission of the People\u2019s Republic of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018684","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Glucocorticoids serve as the first-line clinical treatment for asthma; however, 5%\u201310% of asthma patients respond poorly to glucocorticoids, and their underlying mechanism remains unclear. We investigated whether glucocorticoids can induce airway epithelial endoplasmic reticulum (ER) stress-related apoptosis to decrease their efficacy in treating asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a BALB\/c mouse model of OVA-induced asthma and treated the mice with the glucocorticoid dexamethasone. H&amp;amp;E staining, bronchoalveolar lavage assays and lung function tests were performed. We also treated 16HBE cells with dexamethasone and ER stress inhibitors (4\u03bc8C and melatonin). The viability and apoptosis of 16HBE cells were measured by the CCK-8 and TUNEL assays, respectively. The levels of ER stress markers, including ATF6, ATF4, CHOP and XBP1s, were measured by qPCR and Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Dexamethasone decreased airway inflammatory infiltration and Penh values in asthma model mice but seemed to exacerbate airway epithelium defects in the trachea. qPCR revealed that dexamethasone increased ATF4, CHOP and XBP1 mRNA levels in the lungs of asthma model mice. Moreover, dexamethasone increased apoptosis, as determined by TUNEL assays, and upregulated ATF6, ATF4, CHOP, and XBP1s expression, as determined by Western blotting, in 16HBE cells. The ER stress inhibitors 4\u03bc8C and melatonin decreased the negative effects of dexamethasone on 16HBE cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Glucocorticoids may injure the airway epithelial barrier via ER stress-related apoptosis in asthma. ER stress inhibition may decrease the negative effects of glucocorticoids on the airway epithelial barrier and consequently improve the efficacy of glucocorticoids in asthma. This study proposes a novel potential explanation for glucocorticoid resistance and justify further clinical investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1771751","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:41:06Z","timestamp":1778215266000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Glucocorticoids injure the airway epithelial barrier via endoplasmic reticulum stress-related apoptosis in asthma"],"prefix":"10.3389","volume":"17","author":[{"given":"Hao","family":"You","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Municipal Health Commission Key Laboratory of 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