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FPS-ZM1 inhibits LPS-induced microglial inflammation by suppressing JAK/STAT signaling pathway

文献类型：期刊论文

作者Wang, Lan1,2; Zhao, Danfeng2; Wang, Huan2; Wang, Lele1,2; Liu, Xiaohui1,2; Zhang, Haiyan1,2
刊名INTERNATIONAL IMMUNOPHARMACOLOGY
出版日期2021-11-01
卷号100页码:12
关键词Inflammation Microglia LPS RNA-seq JAK STAT signaling pathway
ISSN号1567-5769
DOI10.1016/j.intimp.2021.108117
通讯作者Zhang, Haiyan(hzhang@simm.ac.cn)
英文摘要FPS-ZM1 is an inhibitor of the receptor for advanced glycation end products (RAGE). Nevertheless, there are few reports about its direct effects on microglial inflammation, and the underlying molecular mechanisms remain to be clarified. The present study investigated the potential effects of FPS-ZM1 on lipopolysaccharide (LPS)mediated microglial inflammation both in vivo and in vitro, and further elucidated the possible molecular mechanisms of action. FPS-ZM1 decreased LPS-induced overproduction of interleukin-1 beta (IL-1 beta), interleukin6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase 2 (COX-2), in both BV-2 cells and primary microglial cells. FPS-ZM1 (10 mg/kg, i.p.) ameliorated proliferation and activation of microglia in the hippocampus of C57BL/6J mice subjected to LPS challenge (5 mg/kg, i.p.). Meanwhile, overproduction of proinflammatory cytokines IL-1 beta and TNF-alpha in the hippocampus was alleviated after treatment with FPS-ZM1. RNA-Sequencing (RNA-Seq) analysis showed involvement of Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway in the regulation of FPS-ZM1 on LPS-induced microglial inflammation. Further investigations demonstrated that FPS-ZM1 downregulated LPS-mediated increases in the phosphorylation levels of JAK/STAT both in vivo and in vitro. FPS-ZM1 also suppressed the nuclear translocation of transcription factor STAT1/3/5 in BV-2 cells. In addition, inhibition of JAK/STAT signaling pathway had an anti-inflammatory effect similar to FPS-ZM1 treatment. Taken together, our results verified the inhibitory effects of FPS-ZM1 against LPS-stimulated microglial inflammation, and for the first time demonstrated such antiinflammatory activities on microglia are associated with regulation of JAK/STAT signaling pathway both in vivo and in vitro, which may shed new light on the pharmacological mechanisms of FPS-ZM1 against microglial inflammation.
WOS关键词NF-KAPPA-B ; OXIDATIVE STRESS ; NEUROINFLAMMATION ; ACTIVATION ; EXPRESSION ; RECEPTOR
资助项目National Natural Science Foundation of China[81872859]
WOS研究方向Immunology ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000705609300007
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/298454]  
专题新药研究国家重点实验室
通讯作者Zhang, Haiyan
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Lan,Zhao, Danfeng,Wang, Huan,et al. FPS-ZM1 inhibits LPS-induced microglial inflammation by suppressing JAK/STAT signaling pathway[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2021,100:12.
APA Wang, Lan,Zhao, Danfeng,Wang, Huan,Wang, Lele,Liu, Xiaohui,&Zhang, Haiyan.(2021).FPS-ZM1 inhibits LPS-induced microglial inflammation by suppressing JAK/STAT signaling pathway.INTERNATIONAL IMMUNOPHARMACOLOGY,100,12.
MLA Wang, Lan,et al."FPS-ZM1 inhibits LPS-induced microglial inflammation by suppressing JAK/STAT signaling pathway".INTERNATIONAL IMMUNOPHARMACOLOGY 100(2021):12.

入库方式： OAI收割

来源：上海药物研究所

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