The First Affiliated Hospital of Jiamusi University, Department of Anesthesiology, China.
PLA General Hospital Eighth Medical Center, Tuberculosis Department one ward, China.
J Toxicol Sci. 2024;49(10):435-446. doi: 10.2131/jts.49.435.
Neuroinflammation plays a critical role in various neurological disorders. Oxycodone has anti-inflammatory properties. The purpose of this work was to look into the effect of oxycodone in controlling lipopolysaccharide (LPS)-induced neuroinflammation in microglia.
LPS-induced HMC3 cells were subjected to oxycodone (2.5, 5, 10 and 20 μg/mL). The mRNA and protein expressions were examined by qRT-PCR and western blotting. TNF-α, IL-1β, IL-6, and IL-8 levels were assessed by ELISA. MTT assay was adopted to measure cell viability. The interactions between CREB, miR-181c and PDCD4 were analyzed by dual-luciferase reporter assay, ChIP and/or RIP assays.
Oxycodone treatment alleviated LPS-induced inflammation in HMC3 cells and increased p-CREB level, but reduced PDCD4 and iNOS levels in LPS-treated cells. Mechanistically, oxycodone mitigated LPS-induced neuroinflammation by upregulating miR-181c. In addition, CREB promoted miR-181c expression by directly binding to the MIR181C promoter, and miR-181c inhibited PDCD4 expression by directly binding to PDCD4 3'UTR. As expected, oxycodone alleviated LPS-induced neuroinflammation by regulating the CREB/miR-181c/PDCD4 axis.
Oxycodone attenuated LPS-induced neuroinflammation in microglia by regulating the CREB/miR-181c/PDCD4 axis. These findings proved that oxycodone is a potential drug for treating neuroinflammation and elucidate the mechanisms involved.
神经炎症在各种神经疾病中起着关键作用。羟考酮具有抗炎作用。本研究旨在探讨羟考酮在控制小胶质细胞脂多糖（LPS）诱导的神经炎症中的作用。
用 LPS 诱导 HMC3 细胞，然后用羟考酮（2.5、5、10 和 20μg/ml）处理。通过 qRT-PCR 和 Western blot 检测 mRNA 和蛋白表达。通过 ELISA 检测 TNF-α、IL-1β、IL-6 和 IL-8 水平。采用 MTT 法检测细胞活力。通过双荧光素酶报告基因检测、ChIP 和/或 RIP 检测分析 CREB、miR-181c 和 PDCD4 之间的相互作用。
羟考酮治疗减轻了 LPS 诱导的 HMC3 细胞炎症，并增加了 p-CREB 水平，但降低了 LPS 处理细胞中的 PDCD4 和 iNOS 水平。机制上，羟考酮通过上调 miR-181c 减轻 LPS 诱导的神经炎症。此外，CREB 通过直接结合 MIR181C 启动子促进 miR-181c 的表达，miR-181c 通过直接结合 PDCD4 3'UTR 抑制 PDCD4 的表达。正如预期的那样，羟考酮通过调节 CREB/miR-181c/PDCD4 轴减轻 LPS 诱导的神经炎症。
羟考酮通过调节 CREB/miR-181c/PDCD4 轴减轻小胶质细胞 LPS 诱导的神经炎症。这些发现证明了羟考酮是治疗神经炎症的一种潜在药物，并阐明了相关机制。
