Yang Yifan, Geng Yanan, Cheng Xiang, Gao Jiayue, Shi Zibi, Zhao Ming
Department of Pain Medicine, Peking University People's Hospital, Beijing 100044, P.R. China.
Department of Brain Plasticity, Beijing Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
Exp Ther Med. 2023 Feb 3;25(3):123. doi: 10.3892/etm.2023.11822. eCollection 2023 Mar.
Hypoxia and neuroinflammation are key risk factors involved in various pathophysiological neural disorders. Hypoxia can aggravate neuroinflammation and ; however, the underlying mechanisms remain unknown. In the present study, hypoxia [either 3 or 1% oxygen (O)] increased lipopolysaccharide (LPS)-induced expression of the IL-6, IL-1β and TNF-α proinflammatory cytokines in BV2 cells. At the molecular level, both hypoxia and FG-4592, an hypoxia inducible factor 1 pathway activator, effectively induced cyclooxygenase-2 (COX-2) expression. The COX-2 inhibitor celecoxib significantly reduced the expression of cytokines induced by LPS under hypoxic conditions. Additionally, the administration of celecoxib inhibited the activation of microglia as well as cytokine expression in mice administered with hypoxia exposure and LPS injection. The present data demonstrated that COX-2 is involved in the hypoxia-induced aggravation of neuroinflammation stimulated by LPS.
缺氧和神经炎症是多种神经病理生理紊乱所涉及的关键风险因素。缺氧可加重神经炎症，然而，其潜在机制仍不清楚。在本研究中，缺氧（3%或1%氧气）增加了脂多糖（LPS）诱导的BV2细胞中白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）促炎细胞因子的表达。在分子水平上，缺氧和缺氧诱导因子1途径激活剂FG-4592均有效诱导环氧化酶-2（COX-2）表达。COX-2抑制剂塞来昔布显著降低了缺氧条件下LPS诱导的细胞因子表达。此外，给予塞来昔布可抑制缺氧暴露和LPS注射小鼠中小胶质细胞的激活以及细胞因子表达。目前的数据表明，COX-2参与了缺氧诱导的LPS刺激的神经炎症加重过程。
