SM905, an artemisinin derivative, inhibited NO and pro-inflammatory cytokine production by suppressing MAPK and NF-kappa B pathways in RAW 264.7 macrophages

doi:10.1038/aps.2009.138

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	SM905, an artemisinin derivative, inhibited NO and pro-inflammatory cytokine production by suppressing MAPK and NF-kappa B pathways in RAW 264.7 macrophages
	Wang, Jun-xia 2; Hou, Li-fei 2; Yang, Yang 3; Tang, Wei2 ; Li, Ying 1; Zuo, Jian-ping2,3
刊名	ACTA PHARMACOLOGICA SINICA
	2009-10
卷号	30 期号:10 页码:1428-1435
关键词	artemisinin SM905 NO iNOS inflammation MAPK NF-kappa B cyclooxygenase 2 TLR4 receptor
ISSN号	1671-4083
DOI	10.1038/aps.2009.138
文献子类	Article
英文摘要	Aim: To elucidate the anti-inflammatory potentials and underlying mechanisms of SM905, a novel artemisinin derivative, in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Methods: Nitric oxide (NO) generation, cytokine production, and the protein expression levels of inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined using a Griess assay, an enzyme-linked immunosorbent assay (ELISA) and a Western blotting assay, respectively. The mRNA expression was measured using real-time PCR. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, c-jun N-terminal kinase (JNK), and the degradation of IkB alpha were assessed by Western blotting analysis. The nuclear translocation of nuclear factor-kB (NF-kB) was observed using confocal microscopy. Results: Pretreatment with SM905 (0, 0.1, 1, and 10 mu mol/L) suppressed LPS-induced NO, TNF-alpha, IL-1 beta, and IL-6 production, and decreased both protein and mRNA levels of iNOS and COX-2. The mRNA expression of LPS receptor Toll-like receptor 4 (TLR4) and myeloid differentiation protein-2 (MD-2) was not changed, while LPS-induced CD14 expression was slightly reduced after SM905 treatment. SM905 markedly decreased the activation of ERK1/2, p38 and JNK suppressed the degradation of I.Ba, but did not modify the expression of interferon regulatory factor-1 (IRF-1), signal transducer and activator of transcription 1 (STAT1) or interferon-inducible (IP-10). By using confocal microscopy, we further observed that NF-kB was correspondingly inhibited in SM905-treated cells. Conclusion: SM905 inhibited NO and pro-inflammatory cytokine production in LPS-stimulated RAW 264.7 cells and these effects are at least partially mediated through suppression of the MAPK and NF-kB signaling pathways.
资助项目	Shanghai Science and Technology Committee[06DZ19006] ; Chinese Academy of Sciences[SIMM0709QN-01]
WOS关键词	ACTIVATED PROTEIN-KINASE ; NITRIC-OXIDE-SYNTHASE ; EXPERIMENTAL RHEUMATOID-ARTHRITIS ; T-CELL-ACTIVATION ; GENE-EXPRESSION ; IMMUNOSUPPRESSIVE ACTIVITY ; TNF-ALPHA ; SIGNAL-TRANSDUCTION ; IN-VITRO ; INDUCTION
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:3739974
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000270733600007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279105]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Zuo, Jian-ping
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Dept Synthet Chem, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, Shanghai 201203, Peoples R China; 3.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Jun-xia,Hou, Li-fei,Yang, Yang,et al. SM905, an artemisinin derivative, inhibited NO and pro-inflammatory cytokine production by suppressing MAPK and NF-kappa B pathways in RAW 264.7 macrophages[J]. ACTA PHARMACOLOGICA SINICA,2009,30(10):1428-1435.
APA	Wang, Jun-xia,Hou, Li-fei,Yang, Yang,Tang, Wei,Li, Ying,&Zuo, Jian-ping.(2009).SM905, an artemisinin derivative, inhibited NO and pro-inflammatory cytokine production by suppressing MAPK and NF-kappa B pathways in RAW 264.7 macrophages.ACTA PHARMACOLOGICA SINICA,30(10),1428-1435.
MLA	Wang, Jun-xia,et al."SM905, an artemisinin derivative, inhibited NO and pro-inflammatory cytokine production by suppressing MAPK and NF-kappa B pathways in RAW 264.7 macrophages".ACTA PHARMACOLOGICA SINICA 30.10(2009):1428-1435.