Dataset Information

IL-17 Exerts Anti-Apoptotic Effect via miR-155-5p Downregulation in Experimental Autoimmune Encephalomyelitis.

ABSTRACT: Multiple sclerosis is an autoimmune, neurodegenerative disease, affecting mostly young adults and resulting in progressive disability. It is a multifactorial disorder, with important involvement of both cellular and epigenetic components. Among the epigenetic factors, microRNAs are currently intensively investigated in the context of multiple sclerosis. It has been shown that their biogenesis and function may be regulated by various cytokines. IL-17, a hallmark cytokine of Th17 cells, has been thought to function predominantly as a pro-inflammatory factor, leading to increased disease symptoms. However, there are several studies indicating its protective role during inflammatory process. In this work, we have assessed the impact of high-dose IL-17 administration on microRNAs' expression profile during the preclinical stage of EAE. For selected microRNA, we have performed computational analysis of its potential target mRNAs and cellular pathways. Based on results obtained from in silico analysis, we have chosen genes from neurotrophin signaling pathway for further experiments-BDNF, HRAS, and BCL2. Results obtained in this study suggested that high dose of IL-17 exerts protective activity via miR-155-5p downregulation. Increased expression of all studied genes, especially BCL2, indicated a potential anti-apoptotic function of IL-17 during the preclinical phase of EAE.

SUBMITTER: Ksiazek-Winiarek D

PROVIDER: S-EPMC5696500 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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IL-17 Exerts Anti-Apoptotic Effect via miR-155-5p Downregulation in Experimental Autoimmune Encephalomyelitis.

Ksiazek-Winiarek Dominika D Szpakowski Piotr P Turniak Malgorzata M Szemraj Janusz J Glabinski Andrzej A

Journal of molecular neuroscience : MN 20171023 3-4

Multiple sclerosis is an autoimmune, neurodegenerative disease, affecting mostly young adults and resulting in progressive disability. It is a multifactorial disorder, with important involvement of both cellular and epigenetic components. Among the epigenetic factors, microRNAs are currently intensively investigated in the context of multiple sclerosis. It has been shown that their biogenesis and function may be regulated by various cytokines. IL-17, a hallmark cytokine of Th17 cells, has been t ...[more]

PMID: 29063445

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Project description:Background: Interleukin 37 (IL-37), a member of IL-1 family, broadly suppresses inflammation in many pathological conditions by acting as a dual-function cytokine in that IL-37 signals via the extracellular receptor complex IL1-R5/IL-1R8, but it can also translocate to the nucleus. However, whether IL-37 exerts beneficial actions in neuroinflammatory diseases, such as multiple sclerosis, remains to be elucidated. Thus, the goals of the present study were to evaluate the therapeutic effects of IL-37 in a mouse model of multiple sclerosis, and if so, whether this is mediated via the extracellular receptor complex IL-1R5/IL-1R8. Methods: We used a murine model of MS, the experimental autoimmune encephalomyelitis (EAE). We induced EAE in three different single and double transgenic mice (hIL-37tg, IL-1R8 KO, hIL-37tg-IL-1R8 KO) and wild type littermates. We also induced EAE in C57Bl/6 mice and treated them with various forms of recombinant human IL-37 protein. Functional and histological techniques were used to assess locomotor deficits and demyelination. Luminex and flow cytometry analysis were done to assess the protein levels of pro-inflammatory cytokines and different immune cell populations, respectively. qPCRs were done to assess the expression of IL-37, IL-1R5 and IL-1R8 in the spinal cord of EAE, and in blood peripheral mononuclear cells and brain tissue samples of MS patients. Results: We demonstrate that IL-37 reduces inflammation and protects against neurological deficits and myelin loss in EAE mice by acting via IL1-R5/IL1-R8. We also reveal that administration of recombinant human IL-37 exerts therapeutic actions in EAE mice. We finally show that IL-37 transcripts are not up-regulated in peripheral blood mononuclear cells and in brain lesions of MS patients, despite the IL-1R5/IL-1R8 receptor complex is expressed. Conclusions: This study presents novel data indicating that IL-37 exerts therapeutic effects in EAE by acting through the extracellular receptor complex IL-1R5/IL-1R8, and that this protective physiological mechanism is defective in MS individuals. IL-37 may therefore represent a novel therapeutic avenue for the treatment of MS with great promising potential.

Dataset Information

IL-17 Exerts Anti-Apoptotic Effect via miR-155-5p Downregulation in Experimental Autoimmune Encephalomyelitis.

Publications

IL-17 Exerts Anti-Apoptotic Effect via miR-155-5p Downregulation in Experimental Autoimmune Encephalomyelitis.

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