Afshar B, Ganjalikhani-Hakemi M, Khalifezadeh Esfahani Z, Eskandari N, Shaygannajad V, Hosseininasab F et al . Evaluating the Effects of Epigallocatechin-3-Gallate on HIF-1α Protein and RORC Gene Expression in Peripheral Blood Mononuclear Cells in Patients With Multiple Sclerosis. BCN 2021; 12 (4) :533-540
URL:
http://bcn.iums.ac.ir/article-1-1667-en.html
1- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
2- Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Abstract:
Introduction: Multiple Sclerosis (MS) is the chronic inflammation of the Central Nervous System (CNS) and autoimmune disease. MS is most widely considered to be mediated by the activation of myelin-specific T CD4+ cells as well as TH1 and TH17 cells. TH17 cells are involved in the pathogenesis of MS in various manners. HIF-1α and RORC are required for the natural differentiation of TH17; they are essential transcription factors for the evolution of TH17 cells. Numerous studies indicated that Epigallocatechin Gallate (EGCG) presents immunomodulatory and anti-inflammatory effects. This study investigated the effects of EGCG on normoxic HIF-1α and RORC2 expression in PBMCs among MS patients.
Methods: Peripheral Blood Mononuclear Cells (PBMCs) were isolated from the whole blood of new cases of MS. The cells were cultured in the presence of a different concentration of EGCG (25, 50,100μM) for 18 and 48 hours. Next, HIF-1α and RORC2 level expressions were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and Real-Time PCR, respectively.
Results: The results showed that EGCG significantly decreased RORC2 gene expression. EGCG did not affect the level of HIF-1α.
Conclusion: However, EGCG did not influence the level of HIF-1α. Our present data has led us to conclude that EGCG could be considered as an anti-inflammatory agent may serve as an achievable therapeutic agent for MS.
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● Multiple sclerosis is considered chronic inflammation of the Central Nervous System (CNS) and autoimmune disease.
● TH17 cell has been involved in the pathogenesis of MS in various ways. HIF-1α and RORC are required for the natural differentiation of TH17 and are essential transcription factors for the evolution of TH17 cells.
● The results showed that EGCG significantly decreased RORC2 gene expression. However, EGCG did not influence the level of HIF-1α. Our present data has led us to conclude that EGCG could be considered as an anti-inflammatory agent may serve as an achievable therapeutic agent for MS.
● The effect of this extract on reducing the expression of RORC gene expression can be due to decreased phosphorylation of smad2 and Stat3 and downregulation of c-Rel, p65/RelA, NF-AT, BATF, IRF4, which binds to the promoter.
Plain Language Summary
Multiple sclerosis has been defined as chronic inflammation of the central nervous system (CNS) and autoimmune disease that is the most common neurodegenerative disorder in adults. More than 2 million people worldwide suffer from MS. MS is most widely considered to be mediated by activation of myelin-specific cells called TH1 and TH17 that cross the BBB (blood-brain barrier) and initiate a chronic inflammatory response. Two proteins called HIF-1α and RORγt are essential transcription factors for the evolution of TH17 cells. On the other hand, Green tea is one of the most common beverages around the world, made from Camellia sinensis leaves, and believing that it has beneficial effects on the health and wellness of the disease. EGCG is the most biologically active ingredient in green tea and is responsible for many of the pharmacological effects of this tea.The purpose of the present study was to investigate the effect of EGCG on the expression of RORC2 and HIF-1α protein levels in peripheral blood mononuclear cells (PBMCs) of MS patients. The results showed that EGCG significantly decreased RORC2 gene expression. However, EGCG did not influence the level of HIF-1α. Our present data has led us to conclude that EGCG could be considered as an anti-inflammatory agent may serve as an achievable therapeutic agent for MS.
Subject:
Cellular and molecular Neuroscience Received: 2019/12/5 | Accepted: 2021/06/30 | Published: 2021/07/1