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.

Elevated IL-22 in psoriasis plays an anti-apoptotic role in keratinocytes through mediating Bcl-xL/Bax

“…4 b). IL-17A was reported to have an anti-apoptotic effect in experimental autoimmune encephalomyelitis (EAE) or under the other conditions [ 18 , 19 ]. Therefore, we are also very interested in its role in apoptosis in psoriasis and found that IL-17A was dramatically increased in psoriatic lesions (n = 23) vs. HC (n = 12) by RT-qPCR (Fig.…”

IL-17A Neutralization Improves the Neurological Outcome of Mice With Ischemic Stroke and Inhibits Caspase-12-Dependent Apoptosis

“…As an inflammatory cytokine, IL-17A was expressed by various cell types including T H 17 cells, γδT cells, some nonlymphocytic cells, and even astrocytes in the ischemic brain to cause the inflammatory responses (Dessalle et al, 2016 ; Ksiazek-Winiarek et al, 2017 ; Li S. et al, 2017 ). Recently, Qiu et al ( 2017 ) found that low dose of apelin-36 in MCAO rats could inhibit ischemia/reperfusion-induced expression of CCAAT/enhancer binding protein homologous protein (CHOP) and 78-kDa glucose-regulated protein (GRP78), improving the neurological outcomes by alleviating the apoptosis (Wang and Kaufman, 2016 ).…”

“…In addition, Bcl-2 family was involved in both mitochondria and the ER by translocation of Ca 2+ to the mitochondria (Hadley et al, 2018 ). It was summarized in the review that CHOP could increase the expression level of Bax and prevent the expression level of Bcl-2 (Ksiazek-Winiarek et al, 2017 ). Su et al ( 2011 ) suggested, GRP78-mediated ER-stress could down-regulate the expression level of Bcl-2, which mediates mitochondria-dependent cell death (Hadley et al, 2018 ).…”

Plasma Erythropoietin, IL-17A, and IFNγ as Potential Biomarkers of Motor Function Recovery in a Canine Model of Spinal Cord Injury

“…And the blockade of IL-17A function at late phases of experimental autoimmune uveoretinitis (EAU) resulted in significantly neural cell apoptosis and tissue damage (Hu et al 2014 ). Another study also suggested that the high dose of IL-17A administration exerts anti-apoptotic and neuroprotective activity via miR-155-5p downregulation (Ksiazek-Winiarek et al 2017 ). Similarly, IFNγ is also a pleiotropic cytokine that exhibits both detrimental and neuroprotective effects.…”