Altered expression of the plasminogen activation pathway in peripheral blood mononuclear cells in multiple sclerosis: possible pathomechanism of matrix metalloproteinase activation

2013 ◽  
Vol 19 (10) ◽  
pp. 1268-1274 ◽  
Author(s):  
Mathew B Cox ◽  
Nikola A Bowden ◽  
Rodney J Scott ◽  
Jeannette Lechner-Scott
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Plasminogen Activation ◽  
Peripheral Blood Mononuclear ◽  
Activation Pathway ◽  
Mmp9 Expression ◽  
Blood Mononuclear Cells

Background: Multiple sclerosis (MS) is an autoimmune disorder where a breakdown in the integrity of the blood-brain barrier is thought to allow lymphocytes to enter the central nervous system. Objectives: The purpose of this study was to examine gene expression profiles between MS patients and healthy controls to identify genes intimately involved in the pathobiology of MS. Methods: Whole-genome gene expression analysis was performed using peripheral blood mononuclear cells from 39 healthy controls and 37 MS patients, 24 MS patients receiving no disease modifying therapy and 13 MS patients receiving interferon-beta (IFN-beta). Pathway analysis was performed to identify pathways dysregulated in MS. Results: Gene expression profiling of MS identified a signature of predominately immune associated genes. The plasminogen activation pathway contained an over-representation of significantly differentially expressed genes, including matrix metallopeptidase 9 (MMP9). Treatment with IFN-beta ameliorated the over-expression of MMP9, however the expression of two genes, plasminogen activator urokinase (PLAU) and serpin peptidase inhibitor, clade B (ovalbumin), member 2 (SERPINB2), forming part of the plasminogen activation pathway were not affected by IFN-beta therapy. Conclusions: High expression levels of MMP9 have been associated with MS and the breakdown of the blood-brain barrier, while IFN-beta therapy decreases MMP9 expression. We confirm altered MMP9 expression in MS, and identify dysregulation within the plasminogen activation cascade, a pathway involved in the activation of MMP9.

scholarly journals Gene expression of chemokines CX3CL1 and CXCL16 and their receptors, CX3CR1 and CXCR6, in peripheral blood mononuclear cells of patients with relapsing-remitting multiple sclerosis - a pilot study

2020 ◽  
Vol 77 (9) ◽  
pp. 967-973
Author(s):  
Ljiljana Stojkovic ◽  
Aleksandra Stankovic ◽  
Ivan Zivotic ◽  
Evica Dincic ◽  
Dragan Alavantic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Fold Change ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Relapsing Remitting ◽  
Blood Mononuclear Cells

Background/Aim. In vitro and in vivo studies show that CX3CL1 and CXCL16 chemokines and their specific receptors, CX3CR1 and CXCR6, respectively, mediate mechanism of neuroinflammation during the pathogenesis of multiple sclerosis (MS). The aim of this study was to investigate relative messenger ribonucleic acid (mRNA) levels of CX3CL1, CXCL16, CX3CR1 and CXCR6 in peripheral blood mononuclear cells, as potential molecular markers of relapsing-remitting (RR) MS. Methods. The study included 43 unrelated RR MS patients, 20 of them with clinically active disease (relapse) and 23 with clinically stable disease (remission), and 28 unrelated healthy subjects as controls. Real-time polymerase chain reactions (PCR) were performed using TaqMan? gene expression assays. Relative expression (mRNA) level of each target gene in each sample of peripheral blood mononuclear cells was calculated as the mean normalized expression. Results. The levels of CX3CR1 mRNA were significantly higher in clinically active RR MS patients compared to controls [fold change = 1.38, p (Mann-Whitney U test) = 0.009], and significantly lower in clinically stable vs active RR MS patients [fold change = - 1.43, p (t-test) = 0.03]. Stable RR MS patients had significantly higher CXCL16 mRNA levels than controls [fold change = 1.33, p (Mann-Whitney U test) = 0.006]. A trend of increased CXCR6 gene expression was found in active RR MS patients compared to controls [fold change = 1.23, p (Mann-Whitney U test) = 0.08]. In either active or stable RR MS patients there were no significant correlations of the clinical parameters with expression levels of the target genes. Conclusion. The current results show that increased CX3CR1 mRNA levels in peripheral blood mononuclear cells could represent a proinflammatory molecular marker of clinically active RR MS.

scholarly journals Evaluation of the Effect of Epigallocatechin-3-gallate (EGCG) on HIF-1α Protein and RORC Gene Expression in Peripheral Blood Mononuclear Cells of Patients with Multiple Sclerosis

2021 ◽  
Author(s):  
Freshteh Alsahebfosoul ◽  
◽  
Boshra Afshar ◽  
Mazdak Ganjalikhani-Hakemi ◽  
Zahra Khalifezadeh Esfahani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Anti Inflammatory

Background: Multiple sclerosis has been considered as chronic inflammation of the central nervous system (CNS) and autoimmune disease .MS is most widely considered to be mediated by activation of myelin-specific T CD4+ cells as well as TH1 and TH17 cells. TH17 cell has been involved in the pathogenesis of MS in various ways. HIF-1α and RORC are required for natural differentiation of TH17 and are essential transcription factors for the evolution of TH17 cells. Numerous studies indicate that epigallocatechin gallate (EGCG) has immunomodulatory and anti-inflammatory effects. Aims: This study investigated the effect of EGCG on normoxic HIF-1α and RORC2 expression in PBMCs of MS patients. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of new cases MS patients. The cells cultured in the presence of a different concentration of EGCG (25, 50,100μM) for 18 and 48 hours. Afterward, HIF-1α and RORC2 level expressions were measured by enzyme-linked immunosorbent assay (ELISA) and Real-Time PCR, respectively. Result: The results showed that EGCG significantly decrease 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 serving as an achievable therapeutic agent for MS.

scholarly journals Multi-parameter immune profiling of peripheral blood mononuclear cells by multiplexed single-cell mass cytometry in patients with early multiple sclerosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chotima Böttcher ◽  
Camila Fernández-Zapata ◽  
Stephan Schlickeiser ◽  
Desiree Kunkel ◽  
Axel R. Schulz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Mass ◽  
Healthy Controls ◽  
Mass Cytometry ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

AbstractMultiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). Studies in rodent models demonstrated an association of CNS-infiltrating monocyte-derived macrophages with disease severity. However, little is known about humans. Here, we performed an exploratory analysis of peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and drug-naïve patients with early MS using multiplexed single-cell mass cytometry and algorithm-based data analysis. Two antibody panels comprising a total of 64 antibodies were designed to comprehensively analyse diverse immune cell populations, with particular emphasis on monocytes. PBMC composition and marker expression were overall similar between the groups. However, an increased abundance of CCR7+ and IL-6+ T cells was detected in early MS-PBMCs, whereas NFAT1hiT-bethiCD4+ T cells were decreased. Similarly, we detected changes in the subset composition of the CCR7+ and MIPβhi HLA-DR+ lymphocyte compartment. Only mild alterations were detected in monocytes/myeloid cells of patients with early MS, namely a decreased abundance of CD141hiIRF8hiCXCR3+CD68− dendritic cells. Unlike in Crohn’s disease, no significant differences were found in the monocyte fraction of patients with early MS compared to healthy controls. This study provides a valuable resource for future studies designed to characterise and target diverse PBMC subsets in MS.

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