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

摘要

Retinoic acid-induced 14 is a developmentally regulated gene induced by retinoic acid and is closely associated with NIK/NF-B 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--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-B. CoCl2-stimulated U87 cells were used to analyze the effect of RAI14 on mTOR-mediated NF-B inflammatory signaling under chemical hypoxia. LPS and TNF- 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-B pathway. Treatment with an mTOR inhibitor (everolimus) ameliorated NF-B activity and IKK/ phosphorylation via RAI14 signaling. Notably, RAI14 also enhanced mTOR-mediated NF-B 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.