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- Title
Neuroprotective effects of cyclooxygenase-2 inhibitor celecoxib against toxicity of LPS-stimulated macrophages toward motor neurons.
- Authors
Yong Huang; Jing Liu; Li-zhen Wang; Wei-yu Zhang; Xing-zu Zhu
- Abstract
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. After macrophages were stimulated with lipopolysaccharide (LPS)+interferon-γ (IFN-γ) 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-γ for 12 h or 24 h, the release of prostaglandin E2 (PGE2), nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) 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-α and IL-1β in macrophages were determined by reverse transcription-polymerase chain reaction after macrophages were stimulated for 6 h and 12 h. 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 PGE2, NO, TNF-α and IL-1β from macrophages were attenuated by pre-treatment with celecoxib. However, celecoxib showed no effect on the ROS levels upregulated by LPS+IFN-γ in the macrophage supernatant. The mRNA levels of COX-2, iNOS, TNF-α and IL-1β were increased inLPS-activated macrophages and, except COX-2, reduced by pre-treatment with celecoxib. 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.
- Publication
Acta Pharmacologica Sinica, 2005, Vol 26, Issue 8, p952
- ISSN
1671-4083
- Publication type
Academic Journal
- DOI
10.1111/j.1745-7254.2005.00136.x