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Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to Traumatic Brain Injury

Wicher, Grzegorz; Wallenquist, Ulrika; Lei, Ying; Enoksson, Mattias; Li, Xiaofei; Fuchs, Barbara; Abu Hamdeh, Sami; Marklund, Niklas LU ; Hillered, Lars and Nilsson, Gunnar, et al. (2017) In Journal of Neurotrauma 34(22). p.3173-3182
Abstract

Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI... (More)

Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of central nervous system injury and found that expression of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum after 72 h in both human samples and mouse models. Astrocytes and oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in the injured region than wild-type mice and had an altered cytokine/chemokine profile in response to injury. These observations indicate that IL-33 plays a role in neuroinflammation with microglia/macrophages being cellular targets for this interleukin post-TBI.

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published
keywords
Journal Article
in
Journal of Neurotrauma
volume
34
issue
22
pages
3173 - 3182
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:85033369626
ISSN
1557-9042
DOI
10.1089/neu.2016.4900
language
English
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no
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9555d6b2-9052-4270-94d1-c640667f5175
date added to LUP
2018-03-03 17:12:49
date last changed
2018-06-17 05:30:48
@article{9555d6b2-9052-4270-94d1-c640667f5175,
  abstract     = {<p>Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of central nervous system injury and found that expression of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum after 72 h in both human samples and mouse models. Astrocytes and oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in the injured region than wild-type mice and had an altered cytokine/chemokine profile in response to injury. These observations indicate that IL-33 plays a role in neuroinflammation with microglia/macrophages being cellular targets for this interleukin post-TBI.</p>},
  author       = {Wicher, Grzegorz and Wallenquist, Ulrika and Lei, Ying and Enoksson, Mattias and Li, Xiaofei and Fuchs, Barbara and Abu Hamdeh, Sami and Marklund, Niklas and Hillered, Lars and Nilsson, Gunnar and Forsberg-Nilsson, Karin},
  issn         = {1557-9042},
  keyword      = {Journal Article},
  language     = {eng},
  month        = {11},
  number       = {22},
  pages        = {3173--3182},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Journal of Neurotrauma},
  title        = {Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to Traumatic Brain Injury},
  url          = {http://dx.doi.org/10.1089/neu.2016.4900},
  volume       = {34},
  year         = {2017},
}