{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T03:03:20Z","timestamp":1770519800232,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Dysfunction of respiratory epithelial cells is acknowledged as an important pathogenesis of asthma. Tumor necrosis factor\u2010\u03b1 induced protein 8 like\u20102 (TNFAIP8L2 or TIPE2) is a famous suppressor of hyperinflammation, which has been involved in regulating asthma progression, however, its role in pyroptosis and oxidative stress of bronchial epithelial cells is still unclear.<\/jats:p><jats:p>1\u2009\u03bcg\/mL LPS and 50\u2009ng\/mL IL\u201013 was used to induce dysfunction of human bronchial epithelial cells BEAS\u20102B, and TIPE2 expression was detected at different time points\u00a0after incubation. Next, TIPE2 expression vector (pcDNA\u2010TIPE2) was transfected into BEAS\u20102B cells to investigate its involvement in LPS\/IL\u201013\u2010induced pyroptosis and oxidative stress. Then, bioinformatics analysis and co\u2010immunoprecipitation(co\u2010IP) assay were used to verify the binding protein of TIPE2, and rescue experiments were performed to validate the molecular mechanism through which TIPE2 regulated pyroptosis and oxidative stress of BEAS\u20102B cells. Finally, ovalbumin (OVA) was used to establish an asthmatic animal model in Balb\/c female mice, adenovirus\u2010mediated overexpression vector of TIPE2 (Ad\u2010TIPE2) was applied to administrate the asthmatic mice, and the effect of TIPE2 on the progression of asthma was investigated. LPS\/IL\u201013 treatment induced cell death (PI<jats:sup>+<\/jats:sup> cells) and TIPE2 downregulation in a time\u2010dependent manner. LPS\/IL\u201013 treatment promoted NLRP3\u2010mediated pyroptosis, secretion of pro\u2010inflammatory cytokines, and oxidative stress in BEAS\u20102B cells, while overexpression of TIPE2 was able to largely reverse the effect of LPS\/IL\u201013. TIPE2 directly interacted with the E3 ubiquitin ligase \u03b2\u2010Transducin Repeat\u2010containing protein (FBW1A) and positively regulated its expression. Rescue experiments with recombinant ubiquitin protein (Ub) and the ubiquitination inhibitor MG132 demonstrated that F\u2010box and WD repeat protein 1A (FBW1A)\u2010mediated ubiquitination of NLRP3 and C1qbp is required in TIPE2 deficiency\u2010induced pyroptosis, mitochondrial damage and oxidative stress. Overexpression of TIPE2 suppressed NLRP3\u2010mediated pyroptosis and C1qbp\u2010mediated oxidative stress and improved respiratory function and pulmonary tissue damage in vivo. TIPE2 protects asthmatic bronchial epithelial cells from NLRP3\u2010induced pyroptosis and C1qbp\u2010induced oxidative stress by interacting with the E3 ubiquitin ligase FBW1A in vitro and in vivo.<\/jats:p>","DOI":"10.1002\/jbt.70534","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:44:39Z","timestamp":1760114679000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TIPE2 Protects Bronchial Epithelial Cells From Pyroptosis and Oxidative Stress by Interacting With the E3 Ubiquitin Ligase FBW1A in Asthmatic Mice"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3258-7662","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Second Affiliated Hospital of Xi'an JiaoTong University Xi'an Xincheng District 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