Peroxiredoxin 2 activates microglia by interacting with Toll-like receptor 4 after subarachnoid hemorrhage.
Peroxiredoxin 2 activates microglia by interacting with Toll-like receptor 4 after subarachnoid hemorrhage.
复制标题
蛛网膜下腔出血后过氧化还原蛋白 2 通过与 Toll 样受体 4 相互作用激活小胶质细胞
DOI：
10.1186/s12974-018-1118-4
复制
发表时间：
2018-03-19
影响因子：
9.3
通讯作者：
Hang CH
中科院分区：
文献类型：
--
作者：
Lu Y;Zhang XS;Zhang ZH;Zhou XM;Gao YY;Liu GJ;Wang H;Wu LY;Li W;Hang CH
背景过氧化物酶（Peroxiredoxin，Prx）蛋白家族是缺血性脑卒中的重要损伤相关分子模式。由于过氧化物酶2（Prx 2）是第三丰富的红细胞中的蛋白质和第二大蛋白质在脑脊液中的创伤性脑损伤和蛛网膜下腔出血（SAH）的患者，我们评估的作用，细胞外Prx 2的背景下SAH.MethodsWe介绍了一个共培养系统的原代神经元和小胶质细胞。将Prx 2添加到具有氧合血红蛋白（OxyHb）的培养基中以在体外模拟SAH。用乳酸脱氢酶（LDH）法检测神经细胞活力，TUNEL法检测神经细胞凋亡。通过ELISA测量培养基中的炎症因子，并通过qPCR测定其在小胶质细胞中的mRNA水平。Toll样受体4敲除（TLR 4-KO）小鼠用于提供TLR 4-KO小胶质细胞; ST-2825用于抑制MyD 88，并且吡咯烷二硫代氨基甲酸酯（PDTC）用于抑制NF-κB。Western blot分析相关细胞信号。结果SAH后Prx 2与小胶质细胞表面的TLR 4相互作用，通过TLR 4/MyD 88/NF-κB信号通路激活小胶质细胞。促炎因子表达和释放，最终导致神经元凋亡。结论SAH后脑脊液中Prx 2的表达是一种DAMP，通过TLR 4/MyD 88/NF-κB途径激活小胶质细胞，导致神经元凋亡。患者脑脊液中Prx 2可能是脑损伤和预后的潜在指标。
BackgroundPeroxiredoxin (Prx) protein family have been reported as important damage-associated molecular patterns (DAMPs) in ischemic stroke. Since peroxiredoxin 2 (Prx2) is the third most abundant protein in erythrocytes and the second most protein in the cerebrospinal fluid in traumatic brain injury and subarachnoid hemorrhage (SAH) patients, we assessed the role of extracellular Prx2 in the context of SAH.MethodsWe introduced a co-culture system of primary neurons and microglia. Prx2 was added to culture medium with oxyhemoglobin (OxyHb) to mimic SAH in vitro. Neuronal cell viability was assessed by lactate dehydrogenase (LDH) assay, and neuronal apoptosis was determined by TUNEL staining. Inflammatory factors in culture medium were measured by ELISA, and their mRNA levels in microglia were determined by qPCR. Toll-like receptor 4 knockout (TLR4-KO) mice were used to provide TLR4-KO microglia; ST-2825 was used to inhibit MyD88, and pyrrolidine dithiocarbamate (PDTC) was used to inhibit NF-κB. Related cellular signals were analyzed by Western blot. Furthermore, we detected the level of Prx2 in aneurysmal SAH patients’ cerebrospinal fluids (CSF) and compared its relationship with Hunt-Hess grades.ResultsPrx2 interacted with TLR4 on microglia after SAH and then activated microglia through TLR4/MyD88/NF-κB signaling pathway. Pro-inflammatory factors were expressed and released, eventually caused neuronal apoptosis. The levels of Prx2 in SAH patients positively correlated with Hunt-Hess grades.ConclusionsExtracellular Prx2 in CSF after SAH is a DAMP which resulted in microglial activation via TLR4/MyD88/NF-κB pathway and then neuronal apoptosis. Prx2 in patients’ CSF may be a potential indicator of brain injury and prognosis.
登录
查看更多内容
白藜芦醇通过抑制 NLRP3 炎性体激活减轻实验性蛛网膜下腔出血后的早期脑损伤。
影响因子：
4.3
作者：
Zhang X;Wu Q;Zhang Q;Lu Y;Liu J;Li W;Lv S;Zhou M;Zhang X;Hang C
通讯作者：
Hang C
影响因子：
5.6
作者：
Liu, Dong-Ling;Zhao, Li-Xue;Du, Jun-Rong
通讯作者：
Du, Jun-Rong
影响因子：
30.5
作者：
Buttgereit, Anne;Lelios, Iva;Greter, Melanie
通讯作者：
Greter, Melanie
影响因子：
13.5
作者：
Park MH;Jo M;Kim YR;Lee CK;Hong JT
通讯作者：
Hong JT
内源性Toll样受体配体及其生物学意义。
影响因子：
5.3
作者：
Yu L;Wang L;Chen S
通讯作者：
Chen S