Circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and mouse islets
Summary: Perturbation of the β-cell circadian clock causes oxidative stress and secretory failure, and proinflammatory cytokines disrupt the β-cell core clock. We hypothesized that cytokine-mediated clock perturbation in β-cells depends on circadian synchronization status. Cytokine-mediated core clo...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225006923 |
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| Summary: | Summary: Perturbation of the β-cell circadian clock causes oxidative stress and secretory failure, and proinflammatory cytokines disrupt the β-cell core clock. We hypothesized that cytokine-mediated clock perturbation in β-cells depends on circadian synchronization status. Cytokine-mediated core clock mRNA expression in non-synchronized insulin-producing INS-1 cells were potentiated upon synchronization, which were differentially translated into alterations in protein levels. Synchronization sensitized INS-1 cells to cytokine-mediated cytotoxicity, associated with potentiation of NF-κB activity. Inhibition of NF-κB abrogated cytokine-mediated clock gene-expression independent of synchronization status and reversed cytokine-mediated period lengthening. In contrast, in murine islets, cytokines generally reduced core clock mRNA expression independently of synchronization status or NF-κB activity. Synchronization prevented cytokine-mediated cytotoxicity, but not NF-κB activity to a degree comparable to that of KINK-1, while alterations in islet rhythmicity were unaffected by NF-κB inhibition. In conclusion, circadian synchronization differentially modifies cytokine-mediated transcriptomic remodeling and cell death in INS-1 cells and murine islets, depending on NF-κB involvement. |
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| ISSN: | 2589-0042 |