中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
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; Wang, LZ; Zhang, WY; Zhu, XZ
刊名ACTA PHARMACOLOGICA SINICA
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
DOI10.1111/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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