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Imatinib prevents dexamethasone-induced pancreatic β-cell
apoptosis through decreased IL-1β production.
Nattinee Jitprawet, Namoiy Semprasert, Petcharee Maneethorn, Suwattanee Kooptiwut*
Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University
*Corresponding Author E-mail: s_kooptiwut@hotmail.com
Abstract
Objectives: Glucocorticoids (GCs) induce pancreatic ᵦ-cell apoptosis through multiple
mechanisms. Our previous study suggested that GCs promote pancreatic ᵦ-cell
apoptosis by decreasing TXNIP expression. TXNIP has been shown to enhance
IL-1ᵦ production via the inflammasome pathway. The tyrosine kinase inhibitor imatinib
has been reported to protect against dexamethasone-induced pancreatic ᵦ-cell apoptosis.
However, whether imatinib exerts this protective effect by reducing IL-1ᵦ production
remains unclear.
Methods: INS-1 cells were treated with 0.1 μM dexamethasone, with or without 10 μM
imatinib. After 72 hours, cell apoptosis was assessed using Annexin V/PI staining. Protein
expression levels of TXNIP, NLRP3, caspase-1, and IL-1β were analyzed by Western blot.
Results: Dexamethasone significantly increased TXNIP expression compared to the control.
Additionally, dexamethasone treatment led to a significant upregulation of NLRP3,
caspase-1, and IL-1β protein levels. However, co-treatment with imatinib significantly
reduced TXNIP, NLRP3, caspase-1, and IL-1β expression compared to dexamethasone
treatment alone.
Conclusions: Our findings demonstrate that dexamethasone induces pancreatic β-cell apoptosis
by increasing TXNIP expression, activating the inflammasome, and promoting
IL-1β production. Furthermore, imatinib co-treatment mitigates these effects by
reducing TXNIP, inflammasome activation, and IL-1β production. These results suggest
that imatinib protects against dexamethasone-induced pancreatic β-cell apoptosis through
the inhibition of IL-1β production.
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