Abstract：
Neuroinflammation is suggested as one of the potential links between CS-induced neuronal dysfunction. Cigarette smoke (CS) is one of the significant contributors of neuroinflammation, consequently leading to cognitive impairment and neurodegeneration. Microglia are the key resident macrophage cells in the brain with cell surface TLR4 receptor for responding to various stress signals. The CS constituents promote inflammation and oxidative stress in microglia leading to cytotoxicity through the TLR4-MK2 axis. However, the role of MK2 kinase in CS-induced microglial inflammation is not yet clearly understood. Therefore, we have used an MK2 inhibitor, PF-3644022 to study modulation of CS-extract induced oxidative and inflammatory signaling in a mouse microglial cell line, Furthermore, we also evaluated the enzymatic activity of acetylcholinesterase (AChE) on a direct exposure of enzyme with CS. CS exposure led to microglial cytotoxicity and enhanced the level of oxidative stress and proinflammatory cytokine release by microglial cells. The microglial cells pretreated with MK2 inhibitor, PF-3644022 significantly reduced the levels of oxidative stress markers, proinflammatory markers, and improved the level of antioxidant proteins in these cells. In addition, direct exposure of CS showed reduction in the enzymatic activity of AChE.
摘要：
神经炎症被认为是CS诱导的神经元功能障碍之间的潜在联系之一。香烟烟雾（CS）是神经炎症的重要贡献者之一，从而导致认知障碍和神经变性。小胶质细胞是大脑中关键的驻留巨噬细胞，具有细胞表面TLR4受体，可响应各种应激信号。CS成分促进小胶质细胞中的炎症和氧化应激,导致通过TLR4-MK2轴的细胞毒性。然而,MK2激酶在CS诱导的小胶质细胞炎症中的作用尚不清楚.因此,我们使用了MK2抑制剂，PF-3644022研究小鼠小胶质细胞系中CS提取物诱导的氧化和炎症信号的调节，此外，我们还评估了乙酰胆碱酯酶（AChE）直接暴露于CS的酶活性。CS暴露导致小胶质细胞毒性，并增强小胶质细胞的氧化应激水平和促炎细胞因子释放。用MK2抑制剂预处理的小胶质细胞，PF-3644022显著降低氧化应激标志物的水平，促炎标志物，并提高了这些细胞中抗氧化蛋白的水平。此外,CS的直接暴露显示AChE的酶活性降低。
