Alteration in the expression of inflammatory cytokines in primary hippocampal astrocytes in response to MK-801 through ERK1/2 and PI3K signals
Alteration in the expression of inflammatory cytokines in primary hippocampal astrocytes in response to MK-801 through ERK1/2 and PI3K signals
复制标题
通过 ERK1/2 和 PI3K 信号改变原代海马星形胶质细胞中炎症细胞因子表达对 MK-801 的反应
DOI：
10.1016/j.cyto.2020.155366
复制
发表时间：
2021
期刊：
影响因子：
3.8
通讯作者：
Yu Wenjuan
中科院分区：
文献类型：
--
作者：
Zhu Hao;Yang Yu;Zhu Min;Shi Xiao;Ye Le;Zhang Song;Fang Hongwei;Yu Wenjuan
我们先前的研究表明，地佐西平(MK-801)可诱导大鼠的精神分裂症样行为，增强GFAP的表达，并激活原代培养的海马星形胶质细胞。星形胶质细胞在神经炎症中起着至关重要的作用，并在神经系统疾病中产生慢性神经炎症的串扰。然而，MK-801对星形胶质细胞神经炎性反应的影响及其作用机制尚未有详细的研究。为解决这一问题，用ELISA法和实时荧光定量聚合酶链式反应检测了MK-801作用24小时后，在有或没有ERK1/2抑制剂PD98059或PI3K抑制剂LY294002的作用下，海马星形胶质细胞IL-1β、IL-6、肿瘤坏死因子α和IL-10的表达和分泌水平。同时检测细胞的凋亡率、存活率和增殖率。MK-801处理不诱导海马星形胶质细胞的凋亡和增殖，但提高了星形胶质细胞的活力。IL-1β、IL-6和肿瘤坏死因子α的表达和分泌水平升高，而IL-10的表达和分泌水平下降，参与了ERK1/2和PI3K信号的表达和分泌。这些结果提示，海马区星形胶质细胞可能通过ERK1/2和PI3K信号通路调节炎性细胞因子的表达，参与精神分裂症的发病。
Our previous study showed that dizocilpine (MK-801) induced schizophrenia-like behavior in rats, enhanced GFAP expression, and activated primary cultured hippocampal astrocytes. Astrocytes play an essential role in neuroinflammation and contribute to the crosstalk that generates chronic neuro-inflammation in neurological diseases. However, the effects of MK-801 treatment on astrocytic neuroinflammatory responses and its mechanism of action have not been studied in detail. To address this issue, IL1β, IL6, TNFα and IL10 expression and secretion levels were evaluated in hippocampal astrocytes in response to MK-801 for 24 h by ELISA and real-time PCR, with and without pretreatment of either the ERK1/2 inhibitor, PD98059 or the PI3K inhibitor, LY294002. Cell apoptosis, viability, and proliferation were also examined. MK-801 treatment did not induce hippocampal astrocytes apoptosis or proliferation, however, MK-801 enhanced astrocytes viability. Additionally, the expression and secretion levels of IL1β, IL6 and TNFα were elevated, but that of IL10 was decreased, in which ERK1/2 and PI3K signals were involved. These findings suggest that hippocampal astrocytes may regulate the expressions of inflammatory cytokines through ERK1/2 and PI3K signaling pathway to participate in the pathogenesis of schizophrenia.