Pyroptosis is a novel type of programmed cell death associated with the pathogenesis of many inflammatory diseases. Docosahexaenoic acid (DHA) and Arachidonic acid (AA) is widely involved in inflammatory pathological processes. However, the effect and mechanism of DHA and AA on pyroptosis in Kupffer cells are poorly understood. The present study demonstrated that DHA and AA ameliorated lipopolysaccharide (LPS)-induced Kupffer cells pyroptosis by reversing the increased expression of NLRP3 inflammasome complex, GSDMD, IL-1β, IL-18, and PI-stained positive rate. Next, the study revealed that GPR120 silencing eliminated the anti-pyroptosis of DHA and AA in LPS-induced Kupffer cells, suggesting that DHA and AA exerted their effect through GPR120 signaling. Importantly, GPR120 endocytose and binds to NLRP3 under LPS stimulation. Furthermore, co-immunoprecipitation showed that DHA and AA promoted the interaction between GPR120 and NLRP3 in LPS-exposed Kupffer cells, thus inhibiting the self-assembly of NLRP3 inflammasome complex. Finally, the study verified that DHA and AA alleviated hepatic injury through inhibiting Kupffer cells pyroptosis in vivo. The findings indicated that DHA and AA alleviated LPS-induced Kupffer cells pyroptosis via GPR120 interaction with NLRP3, it might become a potential therapeutic approach hepatic injury.

细胞焦亡是一种新型的程序性细胞死亡，与许多炎症性疾病的发病机制有关。二十二碳六烯酸 (DHA) 和花生四烯酸 (AA) 广泛参与炎症病理过程。然而，DHA 和 AA 对 Kupffer 细胞细胞焦亡的影响和机制知之甚少。本研究表明，DHA 和 AA 通过逆转 NLRP3 炎性体复合物、GSDMD、IL-1β、IL-18 和 PI 染色阳性率的增加，改善了脂多糖 (LPS) 诱导的库普弗细胞焦亡。接下来，研究表明 GPR120 沉默消除了 LPS 诱导的库普弗细胞中 DHA 和 AA 的抗焦亡，表明 DHA 和 AA 通过 GPR120 信号传导发挥作用。重要的是，GPR120 在 LPS 刺激下内吞并与 NLRP3 结合。此外，免疫共沉淀表明 DHA 和 AA 促进了 LPS 暴露的 Kupffer 细胞中 GPR120 和 NLRP3 之间的相互作用，从而抑制了 NLRP3 炎症小体复合物的自组装。最后，研究证实DHA和AA通过抑制体内枯否细胞焦亡减轻肝损伤。研究结果表明，DHA 和 AA 通过 GPR120 与 NLRP3 的相互作用减轻 LPS 诱导的 Kupffer 细胞焦亡，它可能成为一种潜在的肝损伤治疗方法。