Thesis

Investigating the function of interleukin-33 (IL-33) in the central nervous system

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Awarding institution
  • University of Strathclyde
Date of award
  • 2015
Thesis identifier
  • T13956
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Background and Purpose: The immunomodulatory cytokine interleukin-33 (IL-33) is a member of the IL-1 cytokine family. Its high level of expression in the central nervous system (CNS) suggests it is likely to play an important role in CNS function. Current research evidence indicates it is involved in the development of several neurological autoimmune diseases, including multiple sclerosis (MS).However, the function of IL-33 in CNS homeostasis under healthy physiological conditions is yet to be clarified. This study therefore aims to further understand the exact function and the underlying mechanism of IL-33 in the CNS through investigating: 1) the regional expression of IL-33 and its receptor ST2 in brain tissues of naïve(healthy) and diseased mice; to compare the expression of IL-33 and ST2 receptors in CNS under healthy and diseased condition and 2) the expression of IL-33 and ST2 in the hippocampal culture cells and the function of IL-33 in the brain under healthy conditions. Experimental Methods: C57BL/6 mice were immunised with myelin oligodendrocyte glycoprotein (MOG) ₃₅₋₅₅ peptide to induce experimental autoimmune encephalomyelitis (EAE) and the controls received PBS injection. Clinical scores were recorded daily. Mice were sacrificed on day 26 and CNS tissues were harvested. Immunohistochemical staining was used to study the expression of IL-33 and ST2 in the brain preparations. To identify further the phenotype of the CNS cells expressing IL-33 and ST2 receptors, primary hippocampal cultures were used. IL-33 and ST2 receptor were identified through dual immunohistochemical staining. In addition, the whole cell patch clamp technique was used to determine whether IL-33 modulates synaptic function. Key Result: Data revealed that the expression level of IL-33 was elevated in the hippocampus, midbrain, hypothalamus and cerebellum of the brain tissue of EAE mice compared to naïve mice. In contrast, ST2 expression was high in naïve mice when compared to EAE mice. However, an unusual cluster of ST2 expression was identified in the EAE brain which was absent in the naïve brain. ST2 was also expressed by both astrocytes and neurons of the primary hippocampal culture. Finally, despite the expression of ST2 by the CNS cells in primary hippocampal cultures, its activation with recombinant IL-33 had no effect on neuronal excitability or synaptic activity. Conclusion: These findings show that the IL-33 and its receptor ST2 are highly expressed in CNS under normal and disease conditions with the ST2 receptor being expressed by both astrocytes and neurons of the CNS. However, our study here shows that IL-33 does not seem to modulate neuronal activity and thus further studies are required to determine the exact role of IL-33 under pathological conditions.
Resource Type
DOI
Date Created
  • 2015
Former identifier
  • 1217349

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