The Nogo/Nogo Receptor (NgR) Signal Is Involved in Neuroinflammation through the Regulation of Microglial Inflammatory Activation*
- Yinquan Fang‡1,
- Jun Yan‡1,
- Chenhui Li‡,
- Xiao Zhou§,
- Lemeng Yao‡,
- Tao Pang‡,
- Ming Yan‡,
- Luyong Zhang‡,
- Lei Mao¶2 and
- Hong Liao‡3
- From the ‡Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China,
- the §Department of Biophysics, Saarland University, Homburg 66421, Germany, and
- the ¶Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
- ↵2 To whom correspondence may be addressed. E-mail: leiching{at}163.com.
- ↵3 To whom correspondence may be addressed. Tel.: 86-25-83271043; Fax: 86-25-83271142; E-mail: hliao{at}cpu.edu.cn.
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↵1 Both authors contributed equally to this work.
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.
Footnotes
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↵* This work was supported by National Natural Science Foundation of China Grants 81070967 and 81271338, Specialized Research Fund for the Doctoral Program of Higher Education of China Grant 20130096110011, and the Initial Fund of China Pharmaceutical University (to H. L.). The authors declare that they have no conflicts of interest with the contents of this article.
- Received July 10, 2015.
- Revision received October 2, 2015.
- © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
