GTS-21 attenuates lipopolysaccharide-induced inflammatory cytokine production in vitro by modulating the Akt and NF-κB signaling pathway through the α7 nicotinic acetylcholine receptor

	GTS-21 attenuates lipopolysaccharide-induced inflammatory cytokine production in vitro by modulating the Akt and NF-κB signaling pathway through the α7 nicotinic acetylcholine receptor
	Ye Yue; Ruoxi Liu; Wenxiang Cheng; Yiping Hua; Jinchao Li; Xiaohua Panc; Jiang Peng; Peng Zhang
刊名	International Immunopharmacology
	2015
英文摘要	Objective-GTS-21, a selective α7 nicotinic acetylcholine receptor agonist, has recently been established as a promising treatment for inflammation. However, the detailed molecular mechanism of GTS-21 in suppressing pro-inflammatory cytokine production is only partially explored. The study aimed to analyze cytokine expression suppressed by GTS-21 with lipopolysaccharide (LPS)-induced inflammation in vitro and to gain insights into the role of Akt/NF-κB signaling pathway in this process.Materials and methods-Cell Counting Kit-8 (CCK-8) assay was performed to detect drug cytotoxicity. RAW 264.7 cells were stimulated with LPS and treated with GTS-21. Interleukin (IL)-1β, IL-6, or tumor necrosis factor (TNF)-α production was detected using enzyme-linked immunosorbent assay. Western blot was used to assess the expression patterns of signal transduction protein. Nuclear translocation of nuclear factor (NF)-κB was analyzed by confocal fluorescence microscopy. In addition, α7 nicotinic acetylcholine receptors (α7 nAChR) were detected on RAW264.7, and the α7 nAChR-specific antagonist was adopted to verify whether the effect of GTS-21 was mediated by α7 nAChR.-Results-The CCK-8 assay showed that GTS-21 did not significantly affect cell proliferation. The production of IL-1β, IL-6, and TNF-α decreased after being treated with GTS-21 in LPS-stimulated RAW 264.7 cells. GTS-21 also suppressed LPS-induced phosphorylation of NF-κBp65, IKKα/β, IκBα, and Akt, as well as NF-κB p65 nuclear translocation. Moreover, α7 nAChR was expressed on the surfaces of RAW264.7 cells, and the α7 nAChR-specific antagonist almost completely prohibited the inhibitory effect of GTS-21 on NF-κB activation.Conclusion-These findings indicate that GTS-21 suppresses LPS-induced inflammation by inhibiting the Akt/NF-κB signal pathway through α7 nAChR. GTS-21 has a potential application in inflammatory disease therapy.
收录类别	SCI
原文出处	http://www.sciencedirect.com/science/article/pii/S1567576915301387
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/7200]
专题	深圳先进技术研究院_医工所
作者单位	International Immunopharmacology
推荐引用方式 GB/T 7714	Ye Yue,Ruoxi Liu,Wenxiang Cheng,et al. GTS-21 attenuates lipopolysaccharide-induced inflammatory cytokine production in vitro by modulating the Akt and NF-κB signaling pathway through the α7 nicotinic acetylcholine receptor[J]. International Immunopharmacology,2015.
APA	Ye Yue.,Ruoxi Liu.,Wenxiang Cheng.,Yiping Hua.,Jinchao Li.,...&Peng Zhang.(2015).GTS-21 attenuates lipopolysaccharide-induced inflammatory cytokine production in vitro by modulating the Akt and NF-κB signaling pathway through the α7 nicotinic acetylcholine receptor.International Immunopharmacology.
MLA	Ye Yue,et al."GTS-21 attenuates lipopolysaccharide-induced inflammatory cytokine production in vitro by modulating the Akt and NF-κB signaling pathway through the α7 nicotinic acetylcholine receptor".International Immunopharmacology (2015).