Department of Neurology, The First Affiliated Hospital of Harbin Medical University, China.
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, China.
Life Sci. 2019 Jun 15;227:101-113. doi: 10.1016/j.lfs.2019.04.031. Epub 2019 Apr 16.
NLRP3 inflammasome has been reported associated with some inflammatory and autoimmune diseases. We previously researches showed that interleukin-23 (IL-23) and interleukin-17 (IL-17) aggravates the ischaemic injury of the brain tissue. However, it is poorly understood whether the NLPR3 inflammasome was involved in regulating and activating the IL-23/IL-17 axis in ischaemic stroke. We aimed to delineate whether the NLRP3 inflammasome signalling provokes the IL-23/IL-17 axis and interleukin-23 receptor (IL-23R) inducing the ischaemia-reperfusion injury of the brain in mice.
The male C57/BL6 mice with experimental transient middle cerebral artery occlusion (tMCAO) were established for cerebral ischaemia-reperfusion injury. MCC950 was utilized as a selective NLRP3 inflammasome inhibitor. NLRP3 inflammasome associated protein, IL-23/IL-17 and IL-23R were detected to investigate their changes in the brain tissue after tMCAO.
MCC950 inhibited the NLRP3 inflammasome, which alleviated the neurological ischaemia-reperfusion injury. Inhibition the NLRP3 inflammasome signalling by treatment with MCC950 decreased the activation of IL-23/IL-17 axis and the expression of IL-23R.
The NLRP3 inflammasome facilitated the injury effect of the IL-23/IL-17 axis, which contributed to the cerebral ischaemia-reperfusion injury. This process was associated with IL-23R. Furthermore, this indicated that the NLRP3 inflammasome, as an important therapeutic target for ischaemic stroke, involves multiple mechanisms in ischaemia-reperfusion injury, and MCC950 is a promising way for clinical treatment.
NLRP3 炎性小体与一些炎症和自身免疫性疾病有关。我们之前的研究表明，白细胞介素 23（IL-23）和白细胞介素 17（IL-17）加重了脑组织的缺血性损伤。然而，尚不清楚 NLPR3 炎性小体是否参与调节和激活缺血性中风中的 IL-23/IL-17 轴。我们旨在阐明 NLRP3 炎性小体信号是否引发 IL-23/IL-17 轴和白细胞介素 23 受体（IL-23R）诱导小鼠脑缺血再灌注损伤。
雄性 C57/BL6 小鼠建立实验性短暂性大脑中动脉闭塞（tMCAO）模型，用于脑缺血再灌注损伤。MCC950 被用作选择性 NLRP3 炎性小体抑制剂。检测 NLRP3 炎性小体相关蛋白、IL-23/IL-17 和 IL-23R，以研究它们在 tMCAO 后脑组织中的变化。
MCC950 抑制 NLRP3 炎性小体，减轻神经缺血再灌注损伤。用 MCC950 抑制 NLRP3 炎性小体信号可降低 IL-23/IL-17 轴的激活和 IL-23R 的表达。
NLRP3 炎性小体促进了 IL-23/IL-17 轴的损伤作用，导致脑缺血再灌注损伤。这一过程与 IL-23R 有关。此外，这表明 NLRP3 炎性小体作为缺血性中风的重要治疗靶点，涉及缺血再灌注损伤中的多种机制，MCC950 是一种有前途的临床治疗方法。
