Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
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
_version_ 1783288311855448064
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
work_keys_str_mv AT gaoyuan il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT luochengliang il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT lilili il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT yeguanghua il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT gaocheng il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT wanghaochen il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT huangwenwen il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT wangtao il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT wangzufeng il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT nihong il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT chenxiping il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure
AT taoluyang il33providesneuroprotectionthroughsuppressingapoptoticautophagicandnfkbmediatedinflammatorypathwaysinaratmodelofrecurrentneonatalseizure