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Cell Mol Neurobiol. 2019 Mar;39(2):241-254. doi: 10.1007/s10571-018-0644-z. Epub 2018 Dec 15.

Retinoic Acid-Induced Protein 14 (RAI14) Promotes mTOR-Mediated Inflammation Under Inflammatory Stress and Chemical Hypoxia in a U87 Glioblastoma Cell Line.

Shen X1,2, Zhang J1,2, Zhang X1,2, Wang Y1,2, Hu Y1,2, Guo J3,4,5.

Author information

1
State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
2
Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
3
State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China. guoj@njucm.edu.cn.
4
Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China. guoj@njucm.edu.cn.
5
Department of Biochemistry and Molecular Biology, Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China. guoj@njucm.edu.cn.

Abstract

Retinoic acid-induced 14 is a developmentally regulated gene induced by retinoic acid and is closely associated with NIK/NF-κB signaling. In the present study, we examined the effect of RAI14 on mTOR-mediated glial inflammation in response to inflammatory factors and chemical ischemia. A U87 cell model of LPS- and TNF-α-induced inflammation was used to investigate the role of RAI14 in glial inflammation. U87 cells were treated with siR-RAI14 or everolimus to detect the correlation between mTOR, RAI14, and NF-κB. CoCl2-stimulated U87 cells were used to analyze the effect of RAI14 on mTOR-mediated NF-κB inflammatory signaling under chemical hypoxia. LPS and TNF-α stimulation resulted in the upregulation of RAI14 mRNA and protein levels in a dose- and time-dependent manner. RAI14 knockdown significantly attenuated the level of pro-inflammatory cytokine via inhibiting the IKK/NF-κB pathway. Treatment with an mTOR inhibitor (everolimus) ameliorated NF-κB activity and IKKα/β phosphorylation via RAI14 signaling. Notably, RAI14 also enhanced mTOR-mediated NF-κB activation under conditions of chemical hypoxia. These findings provide significant insight into the role of RAI14 in mTOR-induced glial inflammation, which is closely associated with infection and ischemia stimuli. Thus, RAI14 may be a potential drug target for the treatment of inflammatory diseases.

KEYWORDS:

Chemical hypoxia; NF-κB; Neuroinflmamation; RAI14; mTOR

PMID:
30554401
DOI:
10.1007/s10571-018-0644-z
[Indexed for MEDLINE]

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