Neuroprotective effects of cyclooxygenase-2 inhibitor celecoxib against toxicity of LPS-stimulated macrophages toward motor neurons
文献类型:期刊论文
作者 | Huang, Y; Liu, J![]() |
刊名 | ACTA PHARMACOLOGICA SINICA
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出版日期 | 2005-08 |
卷号 | 26期号:8页码:952-958 |
关键词 | amyotrophic lateral sclerosis celecoxib macrophage NSC34 cell lipopolysaccharide cyclooxygenase-2 prostaglandin E2 nitric oxide reactive oxygen species |
ISSN号 | 1671-4083 |
DOI | 10.1111/j.1745-7254.2005.00136.x |
文献子类 | Article |
英文摘要 | Aim: To establish an in vitro injured motor neuronal model and investigate the neuroprotective effects and possible mechanism of celecoxib a selective, cyclooxygenase-2 (COX-2) inhibitor, on this model. Methods: After macrophages were stimulated with lipopolysaccharide (LPS)+interferon-gamma (IFN-gamma) in the presence or absence of celecoxib for 24 h, the cell-free supernatant of LPS-stimulated macrophages was transferred to the culture of NSC34 cells. Viability of NSC34 cells was assessed by MTT assay after a further 24 h and 72 h incubation. After macrophages were stimulated by LPS+IFN-gamma for 12 h or 24 h, the release of prostaglandin E-2 (PGE(2)), nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) from macrophages was measured by radioimmunoassay, Griess assay, fluorescence assay and enzyme-linked immunosorbent assay, respectively. The mRNA levels of COX-2, inducible nitric oxide synthase (iNOS), TNF-alpha and IL-1 beta in macrophages were determined by reverse transcription-polymerase chain reaction after macrophages were stimulated for 6 h and 12 h. Results: The supernatant of LPS-stimulated mouse macrophages induced the death of NSC34 cells and celecoxib protected the NSC34 cells against this toxicity. The LPS-induced increases in the release of PGE(2), NO, TNF-alpha and IL-1 beta from macrophages were attenuated by pre-treatment with celecoxib. However, celecoxib showed no effect on the ROS levels upregulated by LPS+IFN-gamma in the macrophage supernatant. The mRNA levels of COX-2, iNOS, TNF-alpha and IL-1 beta were increased in LPS-activated macrophages and, except COX-2, reduced by pre-treatment with celecoxib. Conclusion: An in vitro injured motor neuronal model was established by using the toxicity of LPS-stimulated mouse macrophages toward motor neuronal NSC34 cells. In this model, celecoxib exerted neuroprotective effects on motor neurons via an inhibition of the neurotoxic secretions from activated macrophages. |
WOS关键词 | AMYOTROPHIC-LATERAL-SCLEROSIS ; NITRIC-OXIDE SYNTHASE ; TRANSGENIC MOUSE MODEL ; PROSTAGLANDIN E-2 ; SPINAL-CORD ; BRAIN MACROPHAGES ; GENE-EXPRESSION ; MICROGLIA ; CELLS ; ALS |
WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
语种 | 英语 |
CSCD记录号 | CSCD:2208530 |
WOS记录号 | WOS:000231255700007 |
出版者 | BLACKWELL PUBLISHING |
源URL | [http://119.78.100.183/handle/2S10ELR8/273823] ![]() |
专题 | 药理学第二研究室 药物发现与设计中心 生物技术药物研发中心(筹) 上海中药现代化研究中心 药物安全性评价中心 |
通讯作者 | Zhu, XZ |
作者单位 | Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Shanghai Inst Mat Med,Dept Pharmacol, Shanghai 201203, Peoples R China |
推荐引用方式 GB/T 7714 | Huang, Y,Liu, J,Wang, LZ,et al. Neuroprotective effects of cyclooxygenase-2 inhibitor celecoxib against toxicity of LPS-stimulated macrophages toward motor neurons[J]. ACTA PHARMACOLOGICA SINICA,2005,26(8):952-958. |
APA | Huang, Y,Liu, J,Wang, LZ,Zhang, WY,&Zhu, XZ.(2005).Neuroprotective effects of cyclooxygenase-2 inhibitor celecoxib against toxicity of LPS-stimulated macrophages toward motor neurons.ACTA PHARMACOLOGICA SINICA,26(8),952-958. |
MLA | Huang, Y,et al."Neuroprotective effects of cyclooxygenase-2 inhibitor celecoxib against toxicity of LPS-stimulated macrophages toward motor neurons".ACTA PHARMACOLOGICA SINICA 26.8(2005):952-958. |
入库方式: OAI收割
来源:上海药物研究所
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