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IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure
Interleukin-33 (IL-33) is a novel identified chromatin-associated cytokine of IL-1 family cytokines. It signals through a heterodimer comprised of ST2L and IL-1RAcp, and plays a crucial role in many diseases. However, very little is known about the role and underlying intricate mechanisms of IL-33 i...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742123/ https://www.ncbi.nlm.nih.gov/pubmed/29311813 http://dx.doi.org/10.3389/fnmol.2017.00423 |
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author | Gao, Yuan Luo, Cheng-liang Li, Li-li Ye, Guang-hua Gao, Cheng Wang, Hao-chen Huang, Wen-wen Wang, Tao Wang, Zu-feng Ni, Hong Chen, Xi-ping Tao, Lu-yang |
author_facet | Gao, Yuan Luo, Cheng-liang Li, Li-li Ye, Guang-hua Gao, Cheng Wang, Hao-chen Huang, Wen-wen Wang, Tao Wang, Zu-feng Ni, Hong Chen, Xi-ping Tao, Lu-yang |
author_sort | Gao, Yuan |
collection | PubMed |
description | Interleukin-33 (IL-33) is a novel identified chromatin-associated cytokine of IL-1 family cytokines. It signals through a heterodimer comprised of ST2L and IL-1RAcp, and plays a crucial role in many diseases. However, very little is known about the role and underlying intricate mechanisms of IL-33 in recurrent neonatal seizure (RNS). To determine whether IL-33 plays an important regulatory role, we established a neonatal seizure model in this study. Rats were subjected to recurrent seizures induced by inhaling volatile flurothyl. Recombinant IL-33 or PBS were also administered by intraperitoneally (IP) before surgery, respectively. Here, our current results indicated that RNS contributed to a significant reduction in IL-33 and its specific receptor (ST2L) expressions in cortex. While, in hippocampus, RNS induced an increase in IL-33 and ST2L evidently, compared with Sham group. After injection with IL-33, however, a remarkable increase in total IL-33 was detected both in brain cortex and hippocampus. In addition, IL-33 was mainly co-localized in the nuclear of GFAP(+) astrocytes and the cytoplasm of the Iba-1(+) microglia and IL-33(+)/NeuN(+) merged cells. In parallel, ST2L was expressed mainly in the membrane of GFAP(+) astrocytes, Iba-1(+) microglia and NeuN(+) neurons, respectively. Furthermore, administration of IL-33 improved RNS-induced behavioral deficits, promoted bodyweight gain, and ameliorated spatial learning and memory ability. Moreover, IL-33 pretreatment blocked the activation of NF-κB, resisted inflammatory cytokines IL-1β and TNF-α increase, as well as suppressed apoptosis and autophagy activation after RNS. Collectively, IL-33 provides potential neuroprotection through suppressing apoptosis, autophagy and at least in part by NF-κB-mediated inflammatory pathways after RNS. |
format | Online Article Text |
id | pubmed-5742123 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57421232018-01-08 IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure Gao, Yuan Luo, Cheng-liang Li, Li-li Ye, Guang-hua Gao, Cheng Wang, Hao-chen Huang, Wen-wen Wang, Tao Wang, Zu-feng Ni, Hong Chen, Xi-ping Tao, Lu-yang Front Mol Neurosci Neuroscience Interleukin-33 (IL-33) is a novel identified chromatin-associated cytokine of IL-1 family cytokines. It signals through a heterodimer comprised of ST2L and IL-1RAcp, and plays a crucial role in many diseases. However, very little is known about the role and underlying intricate mechanisms of IL-33 in recurrent neonatal seizure (RNS). To determine whether IL-33 plays an important regulatory role, we established a neonatal seizure model in this study. Rats were subjected to recurrent seizures induced by inhaling volatile flurothyl. Recombinant IL-33 or PBS were also administered by intraperitoneally (IP) before surgery, respectively. Here, our current results indicated that RNS contributed to a significant reduction in IL-33 and its specific receptor (ST2L) expressions in cortex. While, in hippocampus, RNS induced an increase in IL-33 and ST2L evidently, compared with Sham group. After injection with IL-33, however, a remarkable increase in total IL-33 was detected both in brain cortex and hippocampus. In addition, IL-33 was mainly co-localized in the nuclear of GFAP(+) astrocytes and the cytoplasm of the Iba-1(+) microglia and IL-33(+)/NeuN(+) merged cells. In parallel, ST2L was expressed mainly in the membrane of GFAP(+) astrocytes, Iba-1(+) microglia and NeuN(+) neurons, respectively. Furthermore, administration of IL-33 improved RNS-induced behavioral deficits, promoted bodyweight gain, and ameliorated spatial learning and memory ability. Moreover, IL-33 pretreatment blocked the activation of NF-κB, resisted inflammatory cytokines IL-1β and TNF-α increase, as well as suppressed apoptosis and autophagy activation after RNS. Collectively, IL-33 provides potential neuroprotection through suppressing apoptosis, autophagy and at least in part by NF-κB-mediated inflammatory pathways after RNS. Frontiers Media S.A. 2017-12-19 /pmc/articles/PMC5742123/ /pubmed/29311813 http://dx.doi.org/10.3389/fnmol.2017.00423 Text en Copyright © 2017 Gao, Luo, Li, Ye, Gao, Wang, Huang, Wang, Wang, Ni, Chen and Tao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Gao, Yuan Luo, Cheng-liang Li, Li-li Ye, Guang-hua Gao, Cheng Wang, Hao-chen Huang, Wen-wen Wang, Tao Wang, Zu-feng Ni, Hong Chen, Xi-ping Tao, Lu-yang IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure |
title | IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure |
title_full | IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure |
title_fullStr | IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure |
title_full_unstemmed | IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure |
title_short | IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure |
title_sort | il-33 provides neuroprotection through suppressing apoptotic, autophagic and nf-κb-mediated inflammatory pathways in a rat model of recurrent neonatal seizure |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742123/ https://www.ncbi.nlm.nih.gov/pubmed/29311813 http://dx.doi.org/10.3389/fnmol.2017.00423 |
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