IL-33/ST2L Signaling Provides Neuroprotection Through Inhibiting Autophagy, Endoplasmic Reticulum Stress, and Apoptosis in a Mouse Model of Traumatic Brain Injury
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 trau...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2018.00095/full |
| _version_ | 1811257747608436736 |
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| author | Yuan Gao Yuan Gao Ming-yang Zhang Tao Wang Yan-yan Fan Lin-sheng Yu Guang-hua Ye Zu-feng Wang Cheng Gao Hao-chen Wang Cheng-liang Luo Lu-yang Tao |
| author_facet | Yuan Gao Yuan Gao Ming-yang Zhang Tao Wang Yan-yan Fan Lin-sheng Yu Guang-hua Ye Zu-feng Wang Cheng Gao Hao-chen Wang Cheng-liang Luo Lu-yang Tao |
| author_sort | Yuan Gao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T18:02:18Z |
| format | Article |
| id | doaj.art-55b2b1efea9a41c5bf4ffe5250b21347 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-12T18:02:18Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-55b2b1efea9a41c5bf4ffe5250b213472022-12-22T03:22:07ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-04-011210.3389/fncel.2018.00095338594IL-33/ST2L Signaling Provides Neuroprotection Through Inhibiting Autophagy, Endoplasmic Reticulum Stress, and Apoptosis in a Mouse Model of Traumatic Brain InjuryYuan Gao0Yuan Gao1Ming-yang Zhang2Tao Wang3Yan-yan Fan4Lin-sheng Yu5Guang-hua Ye6Zu-feng Wang7Cheng Gao8Hao-chen Wang9Cheng-liang Luo10Lu-yang Tao11Department of Forensic Science, Medical School of Soochow University, Suzhou, ChinaDepartment of Forensic Science, Wenzhou Medical University, Wenzhou, ChinaDepartment of Forensic Science, Medical School of Soochow University, Suzhou, ChinaDepartment of Forensic Science, Medical School of Soochow University, Suzhou, ChinaDepartment of Forensic Science, Wenzhou Medical University, Wenzhou, ChinaDepartment of Forensic Science, Wenzhou Medical University, Wenzhou, ChinaDepartment of Forensic Science, Wenzhou Medical University, Wenzhou, ChinaDepartment of Forensic Science, Medical School of Soochow University, Suzhou, ChinaDepartment of Forensic Science, Medical School of Soochow University, Suzhou, ChinaDepartment of Forensic Science, Medical School of Soochow University, Suzhou, ChinaDepartment of Forensic Science, Medical School of Soochow University, Suzhou, ChinaDepartment of Forensic Science, Medical School of Soochow University, Suzhou, ChinaInterleukin-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.http://journal.frontiersin.org/article/10.3389/fncel.2018.00095/fullautophagyendoplasmic reticulum (ER) stressIL-33-ST2L signalingneurobehavioral deficitstraumatic brain injury |
| spellingShingle | Yuan Gao Yuan Gao Ming-yang Zhang Tao Wang Yan-yan Fan Lin-sheng Yu Guang-hua Ye Zu-feng Wang Cheng Gao Hao-chen Wang Cheng-liang Luo Lu-yang Tao IL-33/ST2L Signaling Provides Neuroprotection Through Inhibiting Autophagy, Endoplasmic Reticulum Stress, and Apoptosis in a Mouse Model of Traumatic Brain Injury Frontiers in Cellular Neuroscience autophagy endoplasmic reticulum (ER) stress IL-33-ST2L signaling neurobehavioral deficits traumatic brain injury |
| title | IL-33/ST2L Signaling Provides Neuroprotection Through Inhibiting Autophagy, Endoplasmic Reticulum Stress, and Apoptosis in a Mouse Model of Traumatic Brain Injury |
| title_full | IL-33/ST2L Signaling Provides Neuroprotection Through Inhibiting Autophagy, Endoplasmic Reticulum Stress, and Apoptosis in a Mouse Model of Traumatic Brain Injury |
| title_fullStr | IL-33/ST2L Signaling Provides Neuroprotection Through Inhibiting Autophagy, Endoplasmic Reticulum Stress, and Apoptosis in a Mouse Model of Traumatic Brain Injury |
| title_full_unstemmed | IL-33/ST2L Signaling Provides Neuroprotection Through Inhibiting Autophagy, Endoplasmic Reticulum Stress, and Apoptosis in a Mouse Model of Traumatic Brain Injury |
| title_short | IL-33/ST2L Signaling Provides Neuroprotection Through Inhibiting Autophagy, Endoplasmic Reticulum Stress, and Apoptosis in a Mouse Model of Traumatic Brain Injury |
| title_sort | il 33 st2l signaling provides neuroprotection through inhibiting autophagy endoplasmic reticulum stress and apoptosis in a mouse model of traumatic brain injury |
| topic | autophagy endoplasmic reticulum (ER) stress IL-33-ST2L signaling neurobehavioral deficits traumatic brain injury |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2018.00095/full |
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