Abstract:
:Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) cytokine family and an extracellular ligand for the orphan IL-1 receptor ST2. Accumulated evidence shows that the IL-33/ST2 axis plays a crucial role in the pathogenesis of central nervous system (CNS) diseases and injury, including traumatic brain injury (TBI). However, the roles and molecular mechanisms of the IL-33/ST2 axis after TBI remain poorly understood. In this study, we investigated the role of IL-33/ST2 signaling in mouse TBI-induced brain edema and neurobehavioral deficits, and further exploited underlying mechanisms, using salubrinal (SAL), the endoplasmic reticulum (ER) stress inhibitor and anti-ST2L. The increase in IL-33 level and the decrease in ST2L level at injured cortex were first observed at 24 h post-TBI. By immunofluorescent double-labeled staining, IL-33 co-localized in GFAP-positive astrocytes, and Olig-2-positive oligodendrocytes, and predominantly presented in their nucleus. Additionally, TBI-induced brain water content, motor function outcome, and spatial learning and memory deficits were alleviated by IL-33 treatment. Moreover, IL-33 and SAL alone, or their combination prevented TBI-induced the increase of IL-1β and TNF-α levels, suppressed the up-regulation of ER stress, apoptosis and autophagy after TBI. However, anti-ST2L treatment could significantly invert the above effects of IL-33. Together, these data demonstrate that IL-33/ST2 signaling mitigates TBI-induced brain edema, motor function outcome, spatial learning and memory deficits, at least in part, by a mechanism involving suppressing autophagy, ER stress, apoptosis and neuroinflammation.
journal_name
Front Cell Neuroscijournal_title
Frontiers in cellular neuroscienceauthors
Gao Y,Zhang MY,Wang T,Fan YY,Yu LS,Ye GH,Wang ZF,Gao C,Wang HC,Luo CL,Tao LYdoi
10.3389/fncel.2018.00095subject
Has Abstractpub_date
2018-04-25 00:00:00pages
95issn
1662-5102journal_volume
12pub_type
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journal_title:Frontiers in cellular neuroscience
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journal_title:Frontiers in cellular neuroscience
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journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2014.00440
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journal_title:Frontiers in cellular neuroscience
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doi:10.3389/fncel.2015.00484
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doi:10.3389/fncel.2013.00210
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journal_title:Frontiers in cellular neuroscience
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journal_title:Frontiers in cellular neuroscience
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journal_title:Frontiers in cellular neuroscience
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doi:10.3389/fncel.2014.00089
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