Quercetin mitigated LPS-induced PANoptosis in the bursa of Fabricius via the cGAS/STING signaling pathway in broilers

作者：Yiming Zhang, Qihang Jiang, Haodong Hu, S S Li, Jiahong Chu, Fuze She, Shu Li · 发表于：Poultry Science · 年份：2025 · DOI：10.1016/j.psj.2025.106179 · 被引用次数：1 · 研究领域：interferon and immune responses、Inflammasome and immune disorders、Cytokine Signaling Pathways and Interactions

Quercetin (QUE), a natural bioflavonoid with anti-inflammatory and antioxidant properties, regulates immune organ function by enhancing antioxidant capacity and maintaining mitochondrial homeostasis. This study aims to explore whether QUE can mitigate lipopolysaccharide (LPS)-induced PANoptosis in broilers bursal cells via cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. In vivo, White Leghorn chickens were assigned to Control, QUE (10 mg/kg gavage), LPS (0.15 mg/kg intraperitoneal injection), and LPS+QUE groups. In vitro, brolier lymphoma cells (DT40) were treated with LPS (40 μg/mL), QUE (10 μM), or their combination; STING agonist MSA-2 (2 μM) was used to verify pathway involvement. Hematoxylin-Eosin (H&E) staining, TUNEL assay, immunofluorescence, reactive oxygen species (ROS) detection, antioxidant index assays, quantitative real-time PCR (qRT-PCR), and Western blot (WB) were employed to detect factors related to PANoptosis, inflammation, mitochondrial dynamics, mitochondrial metabolism and the cGAS/STING signaling pathway. Results demonstrated that QUE effectively mitigated LPS-induced oxidative stress, mitochondrial dynamics imbalance, and mitochondrial metabolic dysfunction in broiler bursal cells and DT40 cells. Consequently, QUE reduced the release of mitochondrial DNA (mtDNA) into the cytoplasm, suppressed the activation of the cGAS/STING signaling pathway, and ultimately attenuated the occurrence of PANoptosis and inflammatory respons...