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Circadian clock-dependent regulatory mechanisms such as inflammation and epithelial barrier function are gaining more attention due to their therapeutic potential against allergic inflammatory lung diseases. Currently, there are no studies to support whether REV-ERB\u03b1 activation can attenuate Th2 cytokine-induced epithelial barrier dysfunction in human bronchial epithelial cells. We hypothesized that Th2 cytokine-induced epithelial barrier dysfunction may be protected by activating REV-ERB\u03b1. Treatment with Th2 cytokines or HDM significantly reduced the cell impedance, as confirmed by transepithelial electrical resistance (TEER). However, pre-treatment with SR10067 attenuated Th2 cytokine-induced barrier dysfunction, such as decreased permeability, improved TEER, localization of AJC and TJ proteins, and mRNA and protein levels of selected epithelial barrier and circadian clock targets. Overall, we showed for the first time that REV-ERB\u03b1 activation regulates altered epithelial barrier function that may have direct implications for the treatment of asthma and other allergic diseases.<\/jats:p>","DOI":"10.1042\/cs20240064","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T14:20:11Z","timestamp":1725286811000},"page":"1209-1226","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["REV-ERB\u03b1 agonist SR10067 attenuates Th2 cytokine-mediated barrier dysfunction in human bronchial epithelial cells"],"prefix":"10.1042","volume":"138","author":[{"given":"Santhosh\u00a0Kumar","family":"Duraisamy","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6742-3460","authenticated-orcid":false,"given":"Isaac\u00a0Kirubakaran","family":"Sundar","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"2024092509111298800_B1","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1165\/rcmb.2017-0200TR","article-title":"Airway epithelial barrier dysfunction in chronic obstructive pulmonary disease: role of cigarette smoke exposure","volume":"58","author":"Aghapour","year":"2018","journal-title":"Am. 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