IL-33/ST2 Pathway as a Rational Therapeutic Target for CNS Diseases

Du, Lixia; Wang, Yanqing; Hua, Guoqiang; Mi, Wen-Li

doi:10.1016/j.neuroscience.2017.11.028

Cited by 38 publications

(53 citation statements)

References 99 publications

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“…This finding suggests that the serum sST2 level at the acute phase of AIS may be considered as a novel marker for diagnosis and prognosis in stroke. Recently, there has been an increasing focus on the role of IL-33/ST2 signal pathway in the inflammation of CNS diseases [23,24]. We have demonstrated the novel role of IL-33 in the modulation of Th1/Th2 balance and Th17 response after cerebral ischemia in the previous study [12].…”

Section: Discussionmentioning

confidence: 67%

Serum Soluble ST2 as a Novel Inflammatory Marker in Acute Ischemic Stroke

Chen¹,

Ao²,

Yu³

et al. 2018

Clin. Lab.

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Background: Soluble ST2 (sST2) receptor is secreted and detectable in human serum, which acts as a decoy receptor for interleukin (IL)-33 to prevent IL-33-mediated Th2 immune responses. Recently, elevated serum sST2 has been found to be a novel biomarker in cardiovascular diseases such as heart failure and atherosclerosis. Here, we studied the role of sST2 in acute ischemic stroke (AIS) and its relationship with several inflammatory markers. Methods: The study included 112 patients with first-ever acute ischemic stroke, who were admitted within 48 hours after stroke onset. The serum levels of sST2 and IL-33 were measured with ELISA and the severity of AIS patients was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score. The cerebral infarct volume was calculated according to the Pullicino formula based on the cranial CT scan or MRI. High-sensitivity C-reactive protein (hs-CRP) and serum amyloid A protein (SAA) were measured using the latex-enhanced immunoturbidimetric assay. Results: The serum sST2 level was significantly increased in patients with AIS compared to the control patients without AIS. In addition, the concentration of serum sST2 increased with the infarct volume and the severity of AIS evaluated based on the NIHSS score. Furthermore, the sST2 level correlated positively with the inflammatory marker hs-CRP. Conclusions: Our study suggests that sST2 may be used as a novel diagnostic and predicting inflammatory marker in AIS.

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Section: Discussionmentioning

confidence: 67%

Serum Soluble ST2 as a Novel Inflammatory Marker in Acute Ischemic Stroke

Chen¹,

Ao²,

Yu³

et al. 2018

Clin. Lab.

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“…The IL-33/ST2 signaling pathway plays a crucial role in the pathogenesis of cerebrovascular diseases and associated inflammation [5,8,[17][18][19]. ST2, which acts as the only receptor for IL-33, is a member of the toll-like/IL-1-receptor superfamily [20], with the soluble, circulating form (sST2) and transmembrane form (ST2L) occurring due to alternative splicing and 3′ processing at the RNA level [21].…”

Section: Discussionmentioning

confidence: 99%

Serum soluble ST2 is a predictor for poor long-term prognosis after transient ischemic attack and ischemic stroke: a cohort study

Tian¹,

Guo²,

Wang³

et al. 2019

Preprint

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Background: Soluble ST2 (sST2) is a novel inflammation marker for the prediction of adverse outcomes in patients with cardiovascular disease and diabetes mellitus. The aim of the present study was to examine the predictive value of serum sST2 for prognostic outcomes in patients with transient ischemic attack (TIA)/ischemic stroke.Methods: Patients within 24 h after symptom onset were prospectively enrolled based on the TIA/ischemic stroke database of the First Affiliated Hospital of Zhengzhou University. The 1-year prognostic outcomes were composite adverse events (including ischemic and hemorrhagic stroke, myocardial infarction, and all-cause death) and a combination of major disability and death [modified Rankin Scale (mRS), 3-6]. Cox proportional hazard and logistic regression models were used to evaluate the association between serum sST2 and TIA/ischemic stroke prognosis. The C statistic, net reclassiﬁcation index (NRI), and integrated discrimination index (IDI) were used to present improvement in risk classification.Results: Serum sST2 levels were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores. Kaplan-Meier analysis indicated a significantly different risk in composite adverse events between patients with higher and those with lower levels of sST2 ( P =0.006). Serum sST2 was an independent predictor for composite adverse events (HR: 2.517, 95% CI: 1.279-4.956, P =0.008) and major disability or death (OR: 3.126, 95% CI: 1.452-6.728, P =0.004) after multivariate adjustment. The addition of the sST2 to the NIHSS score significantly improved the predictive value for prognostic outcomes in patients with TIA/ischemic stroke (C statistic: 0.021, IDI: 1.91%, P =0.042 for composite adverse events; NRI: 32.82%, P =0.042 for major disability or death).Conclusions: Serum sST2 levels were positively associated with the severity of TIA/ischemic stroke and could independently predict composite adverse events and major disability or death, indicating that sST2 may be a potential prognostic marker for TIA/ischemic stroke.

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“…Collectively, the data indicate that IL-33 likely mediates neuroprotective functions in various brain injury models. However, IL-33-sensitized type 2 inflammation may be pathogenic in the context of infection or autoimmune disorders [72]. [42], and Tregs [73].…”

Section: Central Nervous Systemmentioning

confidence: 99%

Therapeutic Strategies for Targeting IL-33/ST2 Signalling for the Treatment of Inflammatory Diseases

Chen

Tsai

Yang

et al. 2018

Cell Physiol Biochem

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Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses via interaction with its receptor, ST2. Activation of ST2 signalling by IL-33 triggers pleiotropic immune functions in multiple ST2-expressing immune cells, including macrophages, neutrophils, eosinophils, basophils, mast cells, type 2 helper T cells, regulatory T cells, and group 2 innate lymphoid cells. IL-33-mediated effector functions contribute to the tissue inflammatory and reparative responses in various organs including lung, skin, kidney, central nerve system, cardiovascular system, and gastrointestinal system. Endogenous IL-33/ ST2 signaling exhibits diverse immune regulatory functions during progression of different diseases. IL-33 likely functions as a disease sensitizer and plays pathological roles in inflamed tissues in allergic disorders that involve hyperreactive immune responses in the context of skin and pulmonary allergy. However, IL-33 also mediates tissue-protective functions during the recovery phase following tissue injury in the central nerve system and gastrointestinal system. Modulation of the IL-33/ST2 axis, therefore, represents a promising strategy for treating immune disorders that involve dysregulation of the cytokine signalling. In the past two decades, therapeutic strategies blocking IL-33/ST2 have been extensively studied for the treatment of diseases in animal models. In this review, the current progress on the development of therapeutic biologics for targeting IL-33/ST2 signalling in inflammatory diseases is summarized.

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IL-33/ST2 Pathway as a Rational Therapeutic Target for CNS Diseases

Cited by 38 publications

References 99 publications

Serum Soluble ST2 as a Novel Inflammatory Marker in Acute Ischemic Stroke

Serum Soluble ST2 as a Novel Inflammatory Marker in Acute Ischemic Stroke

Serum soluble ST2 is a predictor for poor long-term prognosis after transient ischemic attack and ischemic stroke: a cohort study

Therapeutic Strategies for Targeting IL-33/ST2 Signalling for the Treatment of Inflammatory Diseases

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