文献类型：期刊文献

英文题名：7b, a novel naphthalimide derivative, exhibited anti-inflammatory effects via targeted-inhibiting TAK1 following down-regulation of ERK1/2-and p38 MAPK-mediated activation of NF-κB in LPS-stimulated RAW264.7 macrophages

作者：Shao, Jin[1,2];Li, Yiquan[1,2];Wang, Ziyuan[1,2];Xiao, Mengmeng[1,2];Yin, Peihao[3];Lu, Yanhua[1,2];Qian, Xuhong[1,2];Xu, Yufang[1,2];Liu, Jianwen[1,2]

机构：[1]E China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Oncol, Shanghai, Peoples R China

年份：2013

卷号：17

期号：2

起止页码：216

外文期刊名：INTERNATIONAL IMMUNOPHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000325122200010)】；

基金：This work was supported by the Fundamental Research Funds for the Central Universities and Shanghai Committee of Science and Technology (Grant No. 11DZ2260600).

语种：英文

外文关键词：7b; Anti-inflammatory; TAK1; MAPK; NF-kappa B

摘要：Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as cancers. 7b, a novel naphthalimide-based DNA intercalator, has exhibited anti-inflammatory effects in phorbol12-myristate 13-acetate/phytohemagglutinin (PMA/PHA)-induced inflammatory responses of Jurkat T cells in our previous study. Here, we tried to further investigate its anti-inflammatory potential and the possible underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and primary mouse macrophages. In our current study, ELISA and Real-time PCR revealed that non-toxic doses of 7b reduced the production and expression of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) in LPS-induced RAW264.7 cells and primary mouse macrophages. Moreover, 7b dose-dependently suppressed the production of prostaglandin E-2 (PGE(2)), nitric oxide (NO). Except for COX-I, non-toxic doses of 7b exhibited parallel inhibition of LPS-induced expression of COX-2 and iNOS at both mRNA and protein levels. The molecular mechanism was associated with inhibition of the phosphorylation/degradation of I kappa B-alpha and nuclear translocation of the NF-kappa B p65. Further analysis of upstream mechanisms showed that blocking of NF-kappa B activation by 7b was mediated by inhibiting TAK1-downstream extracellular signal-regulated kinase (ERK1/2) and p38 kinase signal pathway. Taken together, these results indicated that 7b exhibited anti-inflammatory effects by targeting inhibiting TAK1, leading to ERK1/2- and p38 MAPK-mediated inactivation of NF-kappa B in LPS-stimulated RAW264.7 cells, and this would make 7b a strong candidate for further study as anti-inflammatory agent. (C) 2013 Elsevier B.V. All rights reserved.