کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5630153 1580370 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sphk1 mediates neuroinflammation and neuronal injury via TRAF2/NF-κB pathways in activated microglia in cerebral ischemia reperfusion
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Sphk1 mediates neuroinflammation and neuronal injury via TRAF2/NF-κB pathways in activated microglia in cerebral ischemia reperfusion
چکیده انگلیسی


- Inhibition of Sphk1 decreased IL17 production and neuronal injury in a rat model of cerebral ischemia reperfusion.
- Suppression of Sphk1 relieved IL17 production in OGDR microglia and neuronal damage.
- Inhibition of Sphk1 decreased TRAF2 and NFκB in a rat model of cerebral ischemia reperfusion.
- Knockdown of TRAF2 in microglia relieves neuronal injury induced by OGDR.
- Knockdown of NFκB in microglia relieves OGDR induced neuron apoptosis.

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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Neuroimmunology - Volume 305, 15 April 2017, Pages 35-41
نویسندگان
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