scholarly journals Interleukin-6 Gene Promoter-572 C Allele May Play a Role in Rate of Disease Progression in Multiple Sclerosis

2012 ◽  
Vol 13 (10) ◽  
pp. 13667-13679 ◽  
Author(s):  
Jun Yan ◽  
Jia Liu ◽  
Clement Yihao Lin ◽  
Peter A. Csurhes ◽  
Michael P. Pender ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Interleukin 6 ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Gene Promoter ◽  
Slight Reduction ◽  
Healthy Controls ◽  
Promoter Polymorphisms ◽  
Protein Levels

Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. One important mediator of immune responses and inflammation is interleukin-6 (IL-6). Previously, elevated levels of IL-6 in mononuclear cells in blood and in brain tissue from MS patients have been reported. Various polymorphisms in the promoter region of the IL6 gene have also been linked with IL-6 protein levels. In MS, several small studies have investigated whether two IL6 promoter polymorphisms (−597 G>A and −174 G>C) correlate with MS susceptibility, but with varying results. In the present study, we analyzed these polymorphisms, together with an additional polymorphism (−572 G>C) in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different −597 or −174 IL6 promoter alleles or genotypes. There was a slight reduction in the percentage of individuals with MS who carried a C allele at position −572, although this was not significant after correction for multiple comparisons. Interestingly, however, the −572 C allele showed a significant correlation with the MS severity score, suggesting a possible role in disease progression.

Similar pro- and anti-inflammatory cytokine production in the different clinical forms of multiple sclerosis

2001 ◽  
Vol 7 (3) ◽  
pp. 151-156 ◽  
Author(s):  
I Durán ◽  
E M Martínez-Cáceres ◽  
L Brieva ◽  
M Tintoré ◽  
X Montalban
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Primary Progressive Multiple Sclerosis ◽  
Relative Role ◽  
Healthy Controls ◽  
Primary Progressive ◽  
Clinical Forms ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients

Cytokines play an important role in the initiation and maintenance of the inflammatory reaction in multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system. Magnetic resonance imaging evidence supports clinical divergence between forms of multiple sclerosis with relapses and the primary progressive form without relapses, which shows fewer and smaller inflammatory lesions. With the aim of understanding better the relative role of pro-inflammatory and/or anti-inflammatory cytokines in primary progressive multiple sclerosis in comparison to relapsing forms, we analysed in 65 patients (24 primary progressive, 20 relapsing-remitting and 21 secondary progressive) and 29 healthy controls, the production of cytokines (IFN-g, TNF-a, IL-6, IL-10 and IL-12) by peripheral blood mononuclear cells after in vitro stimulation. We found a similar percentage of cytokines producing cells between healthy controls and the different clinical forms of multiple sclerosis patients. Multiple Sclerosis (2001) 7, 151-156

Gene Therapy Approaches in an Autoimmune Demyelinating Disease: Multiple Sclerosis

2020 ◽  
Vol 19 (6) ◽  
pp. 376-385
Author(s):  
Md. A. Islam ◽  
Shoumik Kundu ◽  
Rosline Hassan
Keyword(s):  
Multiple Sclerosis ◽  
Gene Therapy ◽  
Disease Progression ◽  
Demyelinating Disease ◽  
Human Subjects ◽  
Mice Model ◽  
Focal Lesions ◽  
Protective Function ◽  
Monocytes And Macrophages ◽  
Specific Symptoms

Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.

scholarly journals Regulation of CTLA-4 and PD-L1 Expression in Relapsing-Remitting Multiple Sclerosis Patients after Treatment with Fingolimod, IFNβ-1α, Glatiramer Acetate, and Dimethyl Fumarate Drugs

2021 ◽  
Vol 11 (8) ◽  
pp. 721
Author(s):  
Afshin Derakhshani ◽  
Zahra Asadzadeh ◽  
Hossein Safarpour ◽  
Patrizia Leone ◽  
Mahdi Abdoli Shadbad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that is characterized by inflammation which typically results in significant impairment in most patients. Immune checkpoints act as co-stimulatory and co-inhibitory molecules and play a fundamental role in keeping the equilibrium of the immune system. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and Programmed death-ligand 1 (PD-L1), as inhibitory immune checkpoints, participate in terminating the development of numerous autoimmune diseases, including MS. We assessed the CTLA-4 and PD-L1 gene expression in the different cell types of peripheral blood mononuclear cells of MS patients using single-cell RNA-seq data. Additionally, this study outlines how CTLA-4 and PD-L1 expression was altered in the PBMC samples of relapsing-remitting multiple sclerosis (RRMS) patients compared to the healthy group. Finally, it investigates the impact of various MS-related treatments in the CTLA-4 and PD-L1 expression to restrain autoreactive T cells and stop the development of MS autoimmunity.

scholarly journals H3K23/H3K36 hypoacetylation and HDAC1 up-regulation are associated with adverse consequences in obstructive sleep apnea patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yung-Che Chen ◽  
Po-Yuan Hsu ◽  
Chien-Hung Chin ◽  
Chang-Chun Hsiao ◽  
Chia-Wei Liou ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mononuclear Cells ◽  
Gene Promoter ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Reactive Protein ◽  
Primary Snoring ◽  
Obstructive Sleep

AbstractThe aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.

T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls

1996 ◽  
Vol 1 (5) ◽  
pp. 270-278 ◽  
Author(s):  
CM Pelfrey ◽  
LR Tranquill ◽  
AB Vogt ◽  
HF McFarland
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Demyelinating Disease ◽  
T Cell Responses ◽  
Proteolipid Protein ◽  
T Cell Response ◽  
Healthy Controls ◽  
Cell Responses ◽  
Hla Binding ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which autoimmune T lymphocytes reacting with myelin antigens are believed to play a pathogenic role. Since HLA binding is involved in the selection of T cell responses, we have examined PLP peptide binding to HLA DR2, an HLA allele frequently found in MS patients. Both PLP 40–60 and PLP 89–106 show significant, high affinity binding to HLA DR2. We then tested whether responses to PLP peptides 40–60 and 89–106 are elevated in multiple sclerosis patients compared to matched controls. We also analysed T cell responses to MBP 87–106, which is considered to be the immunodominant region of MBP in humans. Here we demonstrate heterogenous T cell responses to PLP 40–60, PLP 89–106 and MBP 87–106 in both MS patients and controls. The overall number of TCL and the HLA restriction of those TCL did not vary significantly in the two groups. PLP 40–60 specific cytolytic TCL were increased in MS patients, whereas healthy controls had increased percentages of cytolytic TCL responding to PLP 89–106 and MBP 87–106. Although the data presented here shows heterogenous responses in T cell numbers, differences in numbers and specificity of cytolytic cells could be involved in the pathogenesis of autoimmune demyelinating disease.

Cytokine analysis in multiple sclerosis by competitive RT - PCR: A decreased expression of IL-10 and an increased expression of TNF-α in chronic progression

1999 ◽  
Vol 5 (5) ◽  
pp. 342-348 ◽  
Author(s):  
Wen-Xin Huang ◽  
Ping Huang ◽  
Hans Link ◽  
Jan Hillert
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Mononuclear Cells ◽  
Interleukin 4 ◽  
Cytokine Gene Expression ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Cytokine Analysis ◽  
Autoimmune Attack

Multiple sclerosis (MS) is an inflammatory, demyelinating disease that is specific to the central nervous system. Cytokines are thought to be key mediators of the autoimmune attack against central nervous system myelin in MS. To investigate the involvement of cytokines in MS, the mRNA levels of interferon gamma (IFN-g), tumor necrosis factor alpha (TNF-a), interleukin-4 (IL-4) and interleukin-10 (IL-10) in peripheral blood mononuclear cells without stimulation in vitro were quantified by a competitive reverse transcription polymerase chain reaction technique. The level of IL-10 specific mRNA was significantly decreased in 47 MS patients compared with 42 healthy controls (P50.0001). TNF-a was significantly increased in MS patients compared with healthy controls (P=0.014), especially in the patients with chronic progressive MS (P=0.0003). Thus we conclude that there are significant in vivo alterations in cytokine gene expression in the periphery in MS.

Systemic upregulation of CD40 and CD40 ligand mRNA expression in multiple sclerosis

2000 ◽  
Vol 6 (2) ◽  
pp. 61-65 ◽  
Author(s):  
Wen-Xin Huang ◽  
Ping Huang ◽  
Jan Hillert
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Cd40 Ligand ◽  
Autoimmune Response ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Organ Specific

It is increasingly clear that the CD40 and CD40 ligand (CD40L) receptor-ligand pair mediates a crucial activation signal in both cell-mediated and humoral immune responses. Here, we detected mRNA levels of CD40 and CD40L in non-stimulated peripheral blood mononuclear cells in 46 patients with multiple sclerosis (MS) and 46 healthy controls by a competitive RT-PCR procedure allowing quantification without previous culture or antigenic stimulation. The levels of CD40 and CD40L mRNA were markedly increased in MS patients (P <0.0001) compared with healthy controls. There was no difference between clinical MS subgroups or stage of disease. Our findings indicate that, although MS is an organ specific disorder an increased signaling via the CD40 and CD40L pathway may be present at the systemic level. The nature of this upregulation, whether primary or secondary to the organ-specific autoimmune response, is yet to be determined. Since interference with CD40/CD40L is an effective way to interfere with autoimmune model diseases such as experimental autoimmune encephalomyelitis, it may be relevant to investigate further the role of these molecules in the pathogenesis of MS.

The association of IL-18 gene promoter polymorphisms and the levels of serum IL-18 on the risk of multiple sclerosis

2016 ◽  
Vol 146 ◽  
pp. 96-101 ◽  
Author(s):  
Gürdal Orhan ◽  
Esra Eruyar ◽  
Semra Öztürk Mungan ◽  
Fikri Ak ◽  
Bensu Karahalil
Keyword(s):  
Multiple Sclerosis ◽  
Gene Promoter ◽  
Promoter Polymorphisms

scholarly journals Interleukin-10 gene promoter variants and susceptibility to diabetic nephropathy; a meta-analysis

2020 ◽  
Vol 10 (4) ◽  
pp. e38-e38
Author(s):  
Gita Mishra ◽  
Sudeep Gautam ◽  
Thavanati Parvathi Kumara Reddy ◽  
Bhaskar VKS Lakkakula
Keyword(s):  
Diabetic Nephropathy ◽  
Web Of Science ◽  
Meta Analysis ◽  
Gene Promoter ◽  
Interleukin 10 ◽  
Healthy Controls ◽  
Promoter Polymorphisms ◽  
Ample Evidence ◽  
Bibliographic Search ◽  
Il10 Promoter

Introduction: Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD) in diabetes patients. There is ample evidence that the inflammatory pathways are central to both diabetes and DN. Several studies that examined the link between the interleukin-10 (IL10) polymorphisms and DN risk yielded conflicting results. Objectives: The purpose of this meta-analysis is to evaluate the associations between IL10 promoter polymorphisms and DN risk. Methods: A bibliographic search was carried out on PubMed, Google scholar and Web of Science from the beginning until July 30, 2020. Association between IL10 promoter variants (-1082 A>G, -819 C>T and -592 C>A) and DN risk were assessed by considering diabetes without nephropathy (DWN) as well as healthy controls. Data were retrieved and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results: For the IL10 -1082 A> G analysis, a total of 4 studies with DWN controls (682 cases and 529 controls) and 5 studies with healthy controls (1025 cases and 1625 controls) were considered. For the IL10 -819 C> T analysis, a total of three studies with DWN controls (9619 cases and 445 controls) and 5 studies with healthy controls (1005 cases and 1537 controls) were considered. For the IL10 -592 C> T analysis, a total of 5 studies with DWN controls (819 cases and 645 controls) and 5 studies with healthy controls (1005 cases and 1537 controls) were considered. In addition, there was no evidence of publication bias for IL10 promoter variants. No substantial association was observed between IL10 promoter variants and DN risk. Conclusion: Our study signifies that polymorphisms of IL10 -1082 A>G, -819 C>T and -592 C>A are not linked with DN risk.

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