title: The Nogo/Nogo Receptor (NgR) Signal Is Involved in Neuroinflammation through the Regulation of Microglial Inflammatory Activation.
abstract: Microglia have been proposed to play a pivotal role in the inflammation response of the CNS by expressing a range of proinflammatory enzymes and cytokines under pathological stimulus. Our previous study has confirmed that Nogo receptor (NgR), an axon outgrowth inhibition receptor, is also expressed on microglia and regulates cell adhesion and migration behavior in vitro. In the present study, we further investigated the proinflammatory effects and possible mechanisms of Nogo on microglia in vitro. In this study, Nogo peptide, Nogo-P4, a 25-amino acid core inhibitory peptide sequence of Nogo-66, was used. We found that Nogo-P4 was able to induce the expression of inducible nitric-oxide synthase and cyclooxygenase-2 and the release of proinflammatory cytokines, including IL-1β, TNF-α, NO, and prostaglandin E2 in microglia, which could be reversed by NEP1-40 (Nogo-66(1-40) antagonist peptide), phosphatidylinositol-specificphospholipase C, or NgR siRNA treatment. After Nogo-P4 stimulated microglia, the phosphorylation levels of NF-κB and STAT3 were increased obviously, which further mediated microglia expressing proinflammatory factors induced by Nogo-P4. Taken together, we concluded that Nogo peptide could directly take part in CNS inflammatory process by influencing the expression of proinflammatory factors in microglia, which were related to the NF-κB and STAT3 signal pathways. Besides neurite outgrowth restriction, the Nogo/NgR signal might be involved in multiple processes in various inflammation-associated CNS diseases.
authors.affiliation: From the Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China.
authors.forename: Yinquan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: From the Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: From the Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Li
authors.affiliation: the Department of Biophysics, Saarland University, Homburg 66421, Germany, and.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.affiliation: From the Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China.
authors.forename: Lemeng
authors.initials: L
authors.lastname: Yao
authors.affiliation: From the Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Pang
authors.affiliation: From the Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.affiliation: From the Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China.
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: the Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China leiching@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Mao
authors.affiliation: From the Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China, hliao@cpu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Liao
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D058851:GPI-Linked Proteins; C587672:IL1B protein, mouse; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D009185:Myelin Proteins; D016328:NF-kappa B; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone
keywords: NF-kappaB; NgR; Nogo peptide; STAT3; microglia; neurodegenerative disease; neuroinflammation