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Our recent study demonstrated that dexamethasone induces pancreatic \u03b2\u2010cell apoptosis by upregulating the expression of tumor necrosis factor\u2010related apoptosis\u2010inducing ligand (TRAIL) and its receptor, death receptor 5 (DR5). We hypothesized that imatinib may protect against dexamethasone\u2010induced pancreatic \u03b2\u2010cell apoptosis by reducing the expression of TRAIL and DR5, thereby favorably modulating downstream effectors in apoptotic pathways. We test this hypothesis by assessing the effects of imatinib on dexamethasone\u2010induced apoptosis in rat insulinoma cell line cells. As anticipated, dexamethasone treatment led to increased TRAIL and DR5 expression, as well as an elevation in superoxide production. Conversely, expression of the TRAIL decoy receptor (DcR1) was decreased. Moreover, key effectors in the extrinsic and intrinsic apoptosis pathways, such as B\u2010cell lymphoma 2 (BCL\u20102) associated X (BAX), nuclear factor kappa B (NF\u2010\u03bab), P73, caspase 8, and caspase 9, were upregulated, while the antiapoptotic protein BCL\u20102 was downregulated. Interestingly and importantly, imatinib at a concentration of 10\u2009\u00b5M reversed the effect of dexamethasone on TRAIL, DR5, DcR1, superoxide production, BAX, BCL\u20102, NF\u2010\u03baB, P73, caspase 3, caspase 8, and caspase 9. Similar effects of imatinib on dexamethasone\u2010induced TRAIL and DR5 expression were also observed in isolated mouse islets. Taken together, our findings suggest that imatinib protects against dexamethasone\u2010induced pancreatic \u03b2\u2010cell apoptosis by reducing TRAIL and DR5 expression and modulating downstream effectors in the extrinsic and intrinsic apoptosis pathways.<\/jats:p>","DOI":"10.1002\/jcb.30450","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T07:56:46Z","timestamp":1691567806000},"page":"1309-1323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Imatinib prevents dexamethasone\u2010induced pancreatic \u03b2\u2010cell apoptosis via decreased TRAIL and DR5"],"prefix":"10.1002","volume":"124","author":[{"given":"Suchanoot","family":"Kutpruek","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Siriraj Hospital Mahidol University Bangkok 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