Clinical Medicine Research Center, Affiliated Hospital 2 of Nantong University, Nantong 226001, People's Republic of China; Jiangsu Key Laboratory of Neurogeneration, Nantong University, Nantong 226001, People's Republic of China.
Clinical Medicine Research Center, Affiliated Hospital 2 of Nantong University, Nantong 226001, People's Republic of China.
Int Immunopharmacol. 2019 May;70:187-200. doi: 10.1016/j.intimp.2019.02.013. Epub 2019 Feb 25.
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a member of the scavenger receptor family, recognizes multiple ligands and participates in several inflammatory responses, but its function within the central nervous system (CNS) remains unclear. In this study, we discovered an increased LOX-1 expression in activated microglia in vivo and in vitro. Employing the specific inhibitors, we found that conditioned medium of necrotic neurons (Necrotic-CM) induced microglial LOX-1 expression through the MAPKs/NF-κB pathway. Silencing LOX-1 inhibited MAPK phosphorylation, NF-κB-p65 nuclear transportation, and pro-inflammatory factor production in microglia exposed to Necrotic-CM. Furthermore, utilizing the conditioned medium of activated microglia (MG-CM), we discovered microglial LOX-1 aggravated the neuroinflammation-induced neuronal apoptosis. Collectively, a LOX-1/MPAKs/NF-κB positive loop might promote microglia activation and drive the vicious cycle of neuroinflammation and neuronal injury.
凝集素样氧化型低密度脂蛋白受体-1（LOX-1）是清道夫受体家族的一员，可识别多种配体并参与多种炎症反应，但它在中枢神经系统（CNS）中的功能尚不清楚。在这项研究中，我们发现在体内和体外激活的小胶质细胞中 LOX-1 的表达增加。使用特异性抑制剂，我们发现坏死神经元的条件培养基（Necrotic-CM）通过 MAPKs/NF-κB 途径诱导小胶质细胞 LOX-1 的表达。沉默 LOX-1 可抑制 MAPK 磷酸化、NF-κB-p65 核转运和小胶质细胞暴露于 Necrotic-CM 时促炎因子的产生。此外，利用激活的小胶质细胞的条件培养基（MG-CM），我们发现小胶质细胞 LOX-1 加重了神经炎症诱导的神经元凋亡。总之，LOX-1/MPAKs/NF-κB 正反馈回路可能促进小胶质细胞的激活，并推动神经炎症和神经元损伤的恶性循环。
