OX40 gene and serum protein expression profiles in patients with Parkinson's disease

Objective: Inflammation of the immune system and the central nervous system has been known as an important predisposing factor for Parkinson's disease (PD). Increased expression of OX40 protein (CD134) is a known factor for increased inflammation and initiation of NF-kappa-B signaling pathway in different diseases. We aimed to investigate the expression of OX40 at the transcript and serum protein levels. Materials and Methods: Twenty individuals with PD and 20 healthy individuals, as controls, were enrolled in this casecontrol study. Expression of OX40 at the transcript level and serum protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays respectively. Results: The mean expression level of OX40 was increased in patients but not at a significant level (P>0.05). Consistently, the mean serum concentration of OX40 showed a mild, but non-significant, increase in the patients (P>0.05). Conclusion: We conclude that OX40 expression at either the transcript or protein level has no diagnostic utility in asymptomatic PD. This shows the need for clinical, cellular and interventional research to detect new robust biomarkers. © 2018 Royan Institute (ACECR). All Rights Reserved

OX40 gene and serum protein expression profiles in patients with Parkinson's disease

Objective: Inflammation of the immune system and the central nervous system has been known as an important predisposing factor for Parkinson's disease (PD). Increased expression of OX40 protein (CD134) is a known factor for increased inflammation and initiation of NF-kappa-B signaling pathway in different diseases. We aimed to investigate the expression of OX40 at the transcript and serum protein levels. Materials and Methods: Twenty individuals with PD and 20 healthy individuals, as controls, were enrolled in this casecontrol study. Expression of OX40 at the transcript level and serum protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays respectively. Results: The mean expression level of OX40 was increased in patients but not at a significant level (P>0.05). Consistently, the mean serum concentration of OX40 showed a mild, but non-significant, increase in the patients (P>0.05). Conclusion: We conclude that OX40 expression at either the transcript or protein level has no diagnostic utility in asymptomatic PD. This shows the need for clinical, cellular and interventional research to detect new robust biomarkers. © 2018 Royan Institute (ACECR). All Rights Reserved

Increased expression of lymphocyte activation gene-3 by regulatory t cells in multiple sclerosis patients with fingolimod treatment Multiple sikleroz hastalarında fingolimod tedavisi sonucu düzenleyici t hücrelerinde lenfosit aktivasyon gen-3 ekspresyonunda artı�

Introduction: Multiple sclerosis (MS) is associated with the failure of peripheral tolerance to self-antigens. Regulatory T cells (Tregs) play a pivotal role in regulating the immune system and inhibiting development of autoimmune diseases. Until now, the effects of fingolimod, an immunomodulator, on different lymphocyte subsets are not fully understood. In this study, we evaluated how fingolimod affects lymphocyte subsets of patients with MS. Material and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 20 MS and 12 healthy subjects. The number of white blood cells (WBCs) was assessed using an automated cell counter system. Circulating CD4+ cells, CD4+ FoxP3+ cells, and CD25+ FoxP3+ LAG-3+ Tregs were analyzed by flow cytometry. LAG-3 expression on CD4+ FoxP3+ cells was also determined using flow cytometry. Results: Our data revealed that fingolimod had a suppressive effect on WBC number in MS patients (P=0.0001). Fingolimod statistically significantly reduced rate of CD4+ cells (P=0.0005), while increased the rate of circulating CD4+ Foxp3+ cells (P=0.014) and LAG-3 expressing Tregs (P=0.004) in MS patients. Moreover, fingolimod enhanced LAG-3 expression on CD25+ FoxP3+ cells of patients with MS (P=0.04). Conclusion: Based on these findings, fingolimod can be considered as one of effective therapeutic approaches for increasing the number of Tregs and modulating abnormal immune responses in patients with MS. © 2019 Turkish Journal of Immunology. All rights reserved

Therapeutic effects of extracellular vesicles from human adipose-derived mesenchymal stem cells on chronic experimental autoimmune encephalomyelitis

Since in cell therapy, there are always concerns about immune rejection, genetic disability, and malignancies, special attention has been paid to extracellular vesicles (EVs) which are secreted by mesenchymal stem cells (MSCs). In the present study, we assessed and compared the therapeutic effects of human adipose-derived mesenchymal stem cells (hADSC) and hADSC-EVs from adipose tissue on experimental autoimmune encephalomyelitis (EAE). After induction of EAE in C57Bl/6 mice, they were treated with hADSCs, hADSC-EVs, or vehicle intravenously. The clinical score of all mice was recorded every other day. Mice were killed at Day 30 and splenocytes were isolated for proliferation assay and determination of the frequency of Treg cells by flow cytometry. Leukocyte infiltration by hematoxylin and eosin, percentages of demyelination areas by luxol fast blue, and mean fluorescence intensity of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) by immunohistochemistry were assessed in the spinal cord. Our results showed that the maximum mean clinical score and myelin oligodendrocyte glycoprotein-induced proliferation of splenocytes in hADSC- and hADSC-EV-treated mice were significantly lower than the control mice (p <.05). We also demonstrated that the frequency of CD4+CD25+Foxp3+ cells was significantly higher in the spleen of hADSC-treated mice than EAE control mice (p =.023). The inflammation score and the percentages of demyelination areas in hADSC- and hADSC-EV-treated groups significantly declined compared with the untreated control group (p <.05). We also showed that there was no significant difference in MFI of MBP and OLIG2 in the spinal cord of studied groups. Overall, we suggest that intravenous administration of hADSC-EVs attenuates the induced EAE through diminishing proliferative potency of T cells, mean clinical score, leukocyte infiltration, and demyelination in a chronic model of multiple sclerosis. © 2020 Wiley Periodicals, Inc

Modulation of Th17 Proliferation and IL-17A Gene Expression by Acetylated Form of Apigenin in Patients with Multiple Sclerosis

The presence of Th17 cells in CNS lesion of MS patients due to their inflammatory cytokines secretion is in line with the deterioration of the disease. Currently, the use of natural compounds with anti-inflammatory properties such as flavonoids have been considered to reduce inflammation in these patients, but the remaining issue is how deliver these compounds to the site of inflammation. Acetylation is a way to better uptake compound by cells and cross through cellular layers with tight junctions. This study aimed to investigate the in vitro effects of the Apigenin 3-Acetate on Th17 cells of MS patients and compare its efficacy with Apigenin and Methyl Prednisolone Acetate. IC50 for Apigenin 3-Acetate, and Methyl Prednisolone Acetate were determined using three healthy volunteers. The peripheral blood mononuclear cells (PBMCs) of five MS patients were isolated and co-cultured with a selected dose of Apigenin, Apigenin 3-Acetate, and Methyl Prednisolone Acetate for 48 hr, and then theproliferation of Th17 cells in isolated PBMCs was assessed by flow cytometry. The levels of RAR-related orphan receptor (RORC) and IL-17A expression were also determined by quantitative real-time PCR. The results showed that Apigenin 3-Acetate inhibited Th17 cells proliferation (P value: 0.018) at 80 µM concentration after 48 hr. Additionally, IL-17A gene expression significantly (P value� 0.0001) inhibited by Apigenin, Apigenin 3-Acetate and Methyl Prednisolone Acetate in 80 µM, 80 µM and 2.5 µM (selected dose in IC50 determination) respectively These results demonstrate that Acetate increases anti-inflammatory effects of Apigenin on Th17 cells. © 2020, © 2020 Taylor & Francis Group, LLC