Sphk1 mediates neuroinflammation and neuronal injury via TRAF2/NF-κB pathways in activated microglia in cerebral ischemia reperfusion.
Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine1-phosphate (S1P), plays an important role in mediating post-stroke neuroinflammation. However, the pathway and mechanism of the Sphk1-mediated inflammatory response remains unknown. In this study, we found that suppression of Sphk1 decreased IL17 production and relieved neuronal damage induced by microglia in cerebral ischemia reperfusion (IR) or in an in vitro oxygen-glucose deprivation reperfusion (OGDR) system. Inhibition of Sphk1 with an inhibitor or siRNA decreased tumor necrosis factor receptor-associated factor 2 (TRAF2) and nuclear factor-kappa B (NF-κB) sequentially in microglia in response to IR or OGDR. Moreover, we also found that after suppression of TRAF2 or NF-κB by siRNA in microglia, reductions in the downstream molecules NF-κB and IL-17 and in neuronal apoptosis were observed in response to OGDR. Taken together, we hypothesize that Sphk1, TRAF2 and NF-κB form an axis that leads to increased IL-17 and neuronal apoptosis. This axis may be a potential therapeutic target to control neuroinflammation in brain IR.
['Su|Danying|D|', 'Cheng|Yuefeng|Y|', 'Li|Shi|S|', 'Dai|Dawei|D|', 'Zhang|Wei|W|', 'Lv|Manhua|M|']
D000818:Animals D000831:Animals, Newborn D002478:Cells, Cultured D004195:Disease Models, Animal D004660:Encephalitis D005947:Glucose D000860:Hypoxia D020244:Infarction, Middle Cerebral Artery D020381:Interleukin-17 D008297:Male D000432:Methanol D017628:Microglia D016328:NF-kappa B D017853:Phosphotransferases (Alcohol Group Acceptor) D011759:Pyrrolidines D051381:Rats D017207:Rats, Sprague-Dawley D015424:Reperfusion D015398:Signal Transduction D013450:Sulfones D047992:TNF Receptor-Associated Factor 2
Neuroinflammation Microglia Sphingosine kinase 1 Interleukin-17