Dariush Haghmorad; Arman Rahimmi; Alireza Pazoki; Fatemeh Namazi; Mohammad Reza Rahmani; Abbas Ali Amini
Abstract
Background: Interferon-b (IFN-β), a glycoprotein released during viral infections, plays a crucial role in modulating T cells involved in multiple sclerosis (MS). CD200 is an immunomodulatory molecule expressed in many cell types, including neurons. It reduces the progression of MS and experimental ...
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Background: Interferon-b (IFN-β), a glycoprotein released during viral infections, plays a crucial role in modulating T cells involved in multiple sclerosis (MS). CD200 is an immunomodulatory molecule expressed in many cell types, including neurons. It reduces the progression of MS and experimental autoimmune encephalomyelitis (EAE) by interacting with CD200R, mainly expressed on myeloid lineage cells. This interaction prevents brain damage and slows the progression of the disease.Objective: This study investigated changes in the expression of CD200 and CD200R genes in the brains of mice induced with EAE.Methods: Female C57B/L6 mice were divided into three distinct groups: 1) EAE-induced and treated with IFN-b, 2) EAE-induced and treated with phosphate-buffered saline (PBS), and 3) a healthy control group. Two weeks after treatment, the mice were euthanized, and whole-brain tissues were used for mRNA extraction. After cDNA synthesis, the expression of CD200 and CD200R genes was evaluated using Taqman Real-Time PCR. Leukocyte infiltration and demyelination were assessed using Hematoxylin and Eosin staining (H&E) as well as Luxol fast blue (LFB).Results: IFN-β treatment significantly reduced disease progression and demyelination. Furthermore, mice treated with IFN-β showed improved weight gain. The findings also indicated no notable change in CD200 gene expression across the groups examined. However, the expression of CD200R decreased in the IFN-β-treated group, but significantly increased in the untreated group.Conclusion: Our findings suggest that IFN-β treatment may decrease CD200R expression by reducing inflammation. Additionally, the elevated expression in the untreated group may explain why EAE is self-limiting.
Aysan Jafari Harandi; Alireza Mirzaee Sedigh; Mitra Ataei; Sepideh Bayrami; Emran Esmaeilzadeh; Mohammad Hossein Sanati
Abstract
Background: The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such ...
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Background: The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such as microRNAs (miRNAs) following therapy in MS patients.Objective: To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ.Methods: Sixty patients with relapsing-remitting MS (RRMS) and 30 healthy controls (HCs) were enrolled. The patients were categorized as untreated (N=20), IFN-β-treated (N=20), and NTZtreated (N=20). For the expression analysis, real-time PCR was performed on the whole blood. The bioinformatic tools were applied for signaling pathways enrichment analysis of miR-20b targetome.Results: The relative expression of miR-20b was significantly downregulated in the untreated patients compared with the HCs (-1.726-fold, p<0.001), while IFN-β-treated and NTZ-treated patients showed no statistical difference compared with the HCs (0.733-fold, p=0.99 for IFN-β and 1.025-fold, p=0.18 for NTZ). This indicates the restoration of miR-20b expression to normal level in the treated patients. Additionally, in silico analysis demonstrated that the Jak–STAT signaling pathway is enriched with miR-20b targets (p<0.0001).Conclusion: Our findings suggest that the positive effects of IFN-β and NTZ in the RRMS patients could be potentially mediated by returning miR-20b expression to baseline.
