IL-1β priming triggers an adaptive stress response that enhances pancreatic β-cell resilience to subsequent cytotoxic inflammatory insult

In this study, we explored the role of IL-1β-mediated hormesis in defending β-cells against dysfunction and death induced by pro-inflammatory cytokines (CYT). Preconditioning β-cells with physiological circulating levels of IL-1β (IL-1βlow) induced a resilient state, protecting them from CYT-induced cell death while preserving glucose-stimulated insulin secretion through hormesis. IL-1βlow-treated INS-1E cells reduced CYT-induced NO secretion by suppressing NF-κB signaling and decreasing iNOS expression, correlating with reduced β-cell death. IL-1βlow conditioning reduced ER stress and upregulated p-eIF2a in response to CYT, thereby enhancing the expression of ER chaperones and biomarkers linked to improved β-cell identity/functionality.本研究探讨了白细胞介素1β（IL-1β）介导的毒物兴奋效应（hormesis）在保护胰岛β细胞免受促炎细胞因子（pro-inflammatory cytokines, CYT）诱导的功能障碍与死亡中的作用。以生理循环浓度的低剂量白细胞介素1β（IL-1βlow）预处理胰岛β细胞，可诱导其产生耐受状态，通过毒物兴奋效应使其免受CYT诱导的细胞死亡，并维持葡萄糖刺激的胰岛素分泌功能。经IL-1βlow处理的INS-1E细胞，可通过抑制核因子κB（NF-κB）信号通路并下调诱导型一氧化氮合酶（iNOS）的表达，减少CYT诱导的一氧化氮（NO）分泌，这与胰岛β细胞死亡减少密切相关。IL-1βlow预处理还可在CYT刺激下减轻内质网应激（ER stress），并上调磷酸化真核翻译起始因子2α（p-eIF2α）的表达，进而增强内质网分子伴侣（ER chaperones）的表达以及与胰岛β细胞身份维持和功能改善相关的生物标志物的表达水平。