INTRODUCTION Neuroinflammation is a key aspect of various injuries and diseases of the central nervous system and brain, including stroke, Alzheimer's, Parkinson's, multiple sclerosis, etc. Phoenixin-14 is a naturally occurring pleiotropic peptide involved in reproduction, anxiety, pain, and other functions. MATERIALS AND METHODS Primary astrocytes were isolated from new-born pups of c57bl/6 mice. The gene expression of GPR173, CHOP, and GADD34 was measured by real-time PCR. Protein expression was assessed by western blot analysis. Secretions of IL-1β and IL-18 were determined by ELISA. RESULTS Phoenixin-14 (PNX-14) is a ligand for the G protein-coupled receptor GPR173, which we demonstrate to be expressed in astrocytes and suppressed by exposure to lipopolysaccharide (LPS). Endoplasmic reticulum (ER) stress resulting from injury or disease leads to the unfolded protein response, which is mediated by the activation of transcription factors including eIF-2α, ATF4, and CHOP, and regulated by GADD34. ER stress also leads to a robust neuroinflammatory response, which is mediated by HMGB1-induced activation of the NLRP3 inflammasome and subsequent production of IL-1β and IL-18. In the present study, we demonstrate that PNX-14 could attenuate LPS-induced ER stress response and NLRP3 inflammasome activation in mouse cerebral astrocytes. Our findings show that PNX-14 could suppress the production of ROS as well as the decrease in SOD induced by LPS. PNX-14 also inhibited HMGB1-mediated NLRP3 inflammasome activation and production of IL-1β and IL-18. Through a GPR173 siRNA knockdown experiment, we further demonstrate that GPR173 knockdown abolished the effects of PNX-14 on LPS-induced NLRP3 expression and IL-18 production. CONCLUSION These findings suggest that PNX-14 may have potential in the treatment of neuroinflammation.

中文翻译：

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phoenixin-14对星形胶质细胞中脂多糖诱导的炎症和炎症小体激活的保护作用。

简介神经炎症是中风，阿尔茨海默氏症，帕金森氏症，多发性硬化症等中枢神经系统和大脑各种损伤和疾病的关键方面。Phoenixin-14是一种天然存在的多效肽，涉及生殖，焦虑，疼痛和其他职能。材料与方法从新生的c57bl / 6小鼠幼崽中分离出原代星形胶质细胞。通过实时PCR测量GPR173，CHOP和GADD34的基因表达。通过蛋白质印迹分析评估蛋白质表达。通过ELISA测定IL-1β和IL-18的分泌。结果Phoenixin-14（PNX-14）是G蛋白偶联受体GPR173的配体，我们证明其在星形胶质细胞中表达，并受脂多糖（LPS）抑制。由损伤或疾病引起的内质网（ER）应激导致未折叠的蛋白质反应，该反应由包括eIF-2α，ATF4和CHOP在内的转录因子的激活介导，并由GADD34调节。内质网应激还导致强烈的神经炎症反应，这是由HMGB1诱导的NLRP3炎性小体激活以及随后产生IL-1β和IL-18介导的。在本研究中，我们证明PNX-14可以减弱LPS诱导的小鼠脑星形胶质细胞内质网应激反应和NLRP3炎性小体活化。我们的发现表明，PNX-14可以抑制ROS的产生以及LPS诱导的SOD的降低。PNX-14还抑制HMGB1介导的NLRP3炎性小体活化以及IL-1β和IL-18的产生。通过GPR173 siRNA敲低实验，我们进一步证明，GPR173敲除消除了PNX-14对LPS诱导的NLRP3表达和IL-18产生的影响。结论这些发现表明PNX-14在神经炎症的治疗中可能具有潜力。