Interleukin-33 ameliorates ischemic brain injury in experimental stroke through promoting Th2 response and suppressing Th17 response

Luo, Yi; Zhou, Yonggang; Xiao, Wei; Liang, Zhenglun; Dai, Jiapei; Weng, Xiufang; Wu, Xue-Ru

doi:10.1016/j.brainres.2014.12.005

Cited by 100 publications

(89 citation statements)

References 42 publications

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“…Isoforms of ST2 and IL‐33 are highly expressed in the brain and spinal cord, suggesting that IL‐33/ST2 may function directly in the central nervous system 12. In a murine model of stroke, IL‐33 signaling through the membrane‐bound form of ST2 has been shown to be neuroprotective through anti‐inflammatory effects 35. In contrast, the circulating soluble form (sST2), which was measured in our study, is thought to antagonize IL‐33 signaling6 and augment neuroinflammation by operating as a decoy receptor.…”

Section: Discussionmentioning

confidence: 99%

Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke

Wolcott

Batra

Bevers

et al. 2017

Ann Clin Transl Neurol

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Objective ST2 is a member of the toll‐like receptor superfamily that can alter inflammatory signaling of helper T‐cells. We investigated whether soluble ST2 (sST2) could independently predict outcome and hemorrhagic transformation (HT) in the setting of stroke.MethodsWe measured sST2 in patients enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. 646 patients had plasma samples collected at the time of hospital admission and 210 patients had a second sample collected 48 h after stroke onset. Functional outcome was assessed using the modified Rankin Scale (mRS), with good and poor outcomes defined as mRS 0‐2 and 3‐6, respectively. HT was classified using ECASS criteria. The relationships between sST2, outcome, and HT were evaluated using multivariable logistic regression, Kaplan–Meier survival analysis and receiver operating characteristic curves.Results646 patients were included in the analysis (mean age 69 years; 44% women), with a median NIHSS of 5 [IQR: 2–12]. The median sST2 level on hospital admission was 35.0 ng/mL [IQR: 25.7–49.8 ng/mL] and at 48 h it was 37.4 ng/mL [IQR 27.9–55.6 ng/mL]. sST2 was independently associated with poor outcome (OR: 2.77, 95% CI: 1.54–5.06; P = 0.003) and mortality (OR: 3.56, 95% CI: 1.58–8.38, P = 0.001) after multivariable adjustment. Plasma sST2 was also associated with hemorrhagic transformation after adjustment for traditional risk factors (OR: 5.58, 95% CI: 1.40–37.44, P = 0.039).InterpretationSoluble ST2 may serve as a prognostic biomarker for outcome and hemorrhagic transformation in patients with acute stroke. ST2 may link neuroinflammation and secondary injury after stroke.

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Section: Discussionmentioning

confidence: 99%

Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke

Wolcott

Batra

Bevers

et al. 2017

Ann Clin Transl Neurol

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“…These observations might be related to the inhibition of NF-κB activation by IL-33, which suppresses the expression of inflammatory cytokines and neutrophil activation related to infiltration (11). IL-33 significantly improved acute stage and delayed acute cerebral I/R injury in mice, and the protective role of IL-33 has been suggested to involve an induced immuno-shift of Th cells from a Th1 to a Th2-type response, as well as suppression of Th17 immune responses (12). Many studies have shown that IL-33 prevents myocardial I/R injury by inhibiting inflammation and cardiocyte apoptosis (13,14).…”

Section: Il-33 Also Functions As An Inflammatory Cytokine To Induce Tmentioning

confidence: 98%

Interleukin-33 Prevents Retinal Ischemia Reperfusion Injury in Rats by Preventing Apoptosis

Xing

Yang

et al. 2016

Iran Red Crescent Med J

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Background: Retinal ischemia reperfusion (RIR) injury is a common pathological process that can result in visual impairment in many ophthalmic diseases. Inflammation and apoptosis play an important role in RIR injury. Objectives: This experimental study was designed to explore the ability of a new cytokine, IL-33, to attenuate RIR injury via an apoptosis-inhibitory mechanism. Methods: From June, 2015 to October, 2015, 40 Sprague-Dawley (SD) rats from Wuhan university in China were divided into the following four groups: normal control group (NCG), RIR injury model group (MG), IL-33 pretreatment group (IL-33), and PBS group

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“…IL-33 undergoes activating cleavage by caspase-1 and interacts with a host of immune cells to shift the neuroinlammatory response towards neuroprotective, anti-inlammatory microglial and Th2 cell phenotypes, increasing the release of anti-inlammatory cytokines IL-4, IL-5, and IL-10, while decreasing the release of pro-inlammatory cytokines like TNF-α [186,187]. IL-33 binds to suppression of tumorigenicity 2 (ST2) receptor, a receptor that can either be expressed on the membranes of astrocytes and microglia to increase microglia phagocytosis or as a soluble receptor [188].…”

Section: Anti-inlammatory Cytokine Interleukin-33mentioning

confidence: 99%

“…Administration of IL-33 in in-vivo and in-vitro models of AIS is associated with improved neurologic scores, smaller infarct volumes, as well as improvements in the level of cerebral edema and neuronal survival with a shift towards protective microglia phenotypes [174,186,187]. IL-33's protective efects, mediated via its ST2 transmembrane receptor, are thought to be partially mediated by IL-10, as IL-33 is known to induce IL-10 production by microglia and IL-10 knockout mice did not experience the protective, infarct shrinking efects of IL-33 administration post-AIS [174].…”

Section: Anti-inlammatory Il-33 In Aismentioning

confidence: 99%

Roles of Pro- and Anti-inflammatory Cytokines in Traumatic Brain Injury and Acute Ischemic Stroke

Dugue¹,

Nath²,

Dugue³

et al. 2017

Mechanisms of Neuroinflammation

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This chapter will introduce the reader to the pathophysiology of two devastating neurologic events, traumatic brain injury (TBI) and acute ischemic stroke (AIS). Here we focus on the role of key pro-inlammatory and anti-inlammatory cytokines. Several experimental interventions have been found to modulate cytokine production and brain injury after AIS or TBI. Here minocycline, biological response modiiers, hormonal therapies, omega-3 faty acids, N-acetylcysteine, and cannabinoids will be discussed. In addition, the role of cytokine-induced inlammasomes in both TBI and AIS will be addressed and followed by discussion of pro-inlammatory cytokines (e.g., TNF-α, IL-1β, IL-18, and IFN-γ). Finally, the main anti-inlammatory cytokines, IL-33, IL-10, IL-6, and IL-4, will be discussed in the context of both TBI and AIS. It should be noted that the role of these cytokines is diverse and the dichotomization of classically pro-versus anti-inlammatory cytokines is being re-examined, as many of these cytokines have been found to play dual roles in TBI and AIS brain injury.Keywords: traumatic brain injury, ischemic stroke, cytokines, interleukins, inlammasome Pathophysiology of traumatic brain injuryTraumatic brain injury (TBI) is a major cause of death and disability worldwide [1,2]. It is one of the most commonly diagnosed neurological disorders in the United States, impacting people of a variety of ages and segments of society [3]. In Europe, the economic cost of © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.TBI is over 33 billion euros per year [4]. Continued surveillance and research is being done to reduce primary and secondary TBI [as well as acute ischemic stroke(AIS)]-induced brain injury [1].The pathophysiology of TBI begins with the initial brain trauma (i.e., the primary injury). This primary injury results from mechanical damage that disrupts the blood-brain barrier (BBB), alters the vasculature and damages brain tissue. The resulting injured glia and neurons release their intracellular contents (i.e., damage-associated molecular paterns; (DAMPs)) into the extracellular space and activate neighboring glia and neurons. Activated glia and neurons then produce molecular signals that can both exacerbate and mend the acute injury and contribute to long-term recovery [5][6][7][8][9]. These downstream molecular and cellular processes (i.e., the secondary injury in TBI) are the focus of many pre-clinical and clinical therapeutic studies. Secondary injury in TBI involves a host of molecular and cellular responses to the The pathophysiology of AIS and TBI share common mechanisms. The initial insult in AIS, an occlusion of blood low resulting in a core infarct zone surrounded by a poorly perfused penumbra, versus the initial primary physical impact in TBI both result in pe...

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Interleukin-33 ameliorates ischemic brain injury in experimental stroke through promoting Th2 response and suppressing Th17 response

Cited by 100 publications

References 42 publications

Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke

Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke

Interleukin-33 Prevents Retinal Ischemia Reperfusion Injury in Rats by Preventing Apoptosis

Roles of Pro- and Anti-inflammatory Cytokines in Traumatic Brain Injury and Acute Ischemic Stroke

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