Neuroinflammation related to microglial activation plays an important role in neurodegenerative diseases. Translocator protein 18 kDa (TSPO), a biomarker of reactive gliosis, its ligands can reduce neuroinflammation and can be used to treat neurodegenerative diseases. Therefore, we explored whether TSPO ligands exert an anti-inflammatory effect by affecting the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, thereby inhibiting the release of inflammatory cytokines in microglial cells. In the present study, BV-2 cells were exposed to lipopolysaccharide (LPS) for 6 h to induce an inflammatory response. We found that the levels of reactive oxygen species (ROS), NLRP3 inflammasome, interleukin-1β (IL-1β), and interleukin-18 (IL-18) were significantly increased. However, pretreatment with TSPO ligands inhibited BV-2 microglial and NLRP3 inflammasome activation and significantly reduced the levels of ROS, IL-1β, and IL-18. Furthermore, a combination of LPS and ATP was used to activate the NLRP3 inflammasome. Both pretreatment and post-treatment with TSPO ligand can downregulate the activation of NLRP3 inflammasome and IL-1β expression. Finally, we found that TSPO was involved in the regulation of NLRP3 inflammasome with TSPO ligands treatment in TSPO knockdown BV2 cells. Collectively, these results indicate that TSPO ligands are promising targets to control microglial reactivity and neuroinflammatory diseases.

与小胶质细胞活化有关的神经炎症在神经退行性疾病中起重要作用。Translocator蛋白18 kDa（TSPO）是反应性神经胶质增生的生物标志物，其配体可减少神经炎症，可用于治疗神经退行性疾病。因此，我们探讨了TSPO配体是否通过影响核苷酸结合域样受体蛋白3（NLRP3）炎性小体来发挥抗炎作用，从而抑制了小胶质细胞中炎性细胞因子的释放。在本研究中，BV-2细胞暴露于脂多糖（LPS）6小时以诱导炎症反应。我们发现活性氧（ROS），NLRP3炎性小体，白介素1β（IL-1β）和白介素18（IL-18）的水平显着增加。然而，TSPO配体预处理可抑制BV-2小胶质细胞和NLRP3炎性小体活化，并显着降低ROS，IL-1β和IL-18的水平。此外，使用LPS和ATP的组合来激活NLRP3炎性小体。用TSPO配体进行的预处理和后处理均可以下调NLRP3炎性小体的激活和IL-1β表达。最后，我们发现TSPO参与了TSPO敲除BV2细胞中TSPO配体处理对NLRP3炎性小体的调控。总的来说，这些结果表明TSPO配体是控制小胶质细胞反应性和神经炎性疾病的有希望的靶标。用TSPO配体进行的预处理和后处理均可以下调NLRP3炎性小体的激活和IL-1β表达。最后，我们发现TSPO参与了TSPO敲除BV2细胞中TSPO配体处理对NLRP3炎性小体的调控。总的来说，这些结果表明TSPO配体是控制小胶质细胞反应性和神经炎性疾病的有希望的靶标。用TSPO配体进行的预处理和后处理均可以下调NLRP3炎性小体的激活和IL-1β表达。最后，我们发现TSPO参与了TSPO敲除BV2细胞中TSPO配体处理对NLRP3炎性小体的调控。总的来说，这些结果表明TSPO配体是控制小胶质细胞反应性和神经炎性疾病的有希望的靶标。