scholarly journals Natalizumab Treatment Modulates Peroxisome Proliferator-Activated Receptors Expression in Women with Multiple Sclerosis

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Véronique Ferret-Sena ◽  
Alexandra Maia e Silva ◽  
Armando Sena ◽  
Inês Cavaleiro ◽  
José Vale ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Peroxisome Proliferator ◽  
Healthy Controls ◽  
Autoimmune Encephalomyelitis ◽  
Peripheral Blood Mononuclear ◽  
Natalizumab Treatment ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome Proliferator-Activated Receptors (PPAR) are transcription factors suggested to be involved in inflammatory lesions of autoimmune encephalomyelitis and multiple sclerosis (MS). Our objective was to assess whether Natalizumab (NTZ) therapy is associated with alterations of PPAR expression in MS patients. We analyzed gene expression of PPAR in peripheral blood mononuclear cells (PBMC) as well as blood inflammatory markers in women with MS previously medicated with first-line immunomodulators (baseline) and after NTZ therapy. No differences in PPARα, PPARβ/δ, PPARγ, and CD36 mRNA expression were found in PBMC between patients under baseline and healthy controls. At three months, NTZ increased PPARβ/δmRNA (p=0.009) in comparison to baseline, while mRNA expression of PPARγand CD36 (a well-known PPAR target gene) was lower in comparison to healthy controls (p=0.026andp=0.028, resp.). Although these trends of alterations remain after six months of therapy, the results were not statistically significant. Osteopontin levels were elevated in patients (p=0.002) and did not change during the follow-up period of NTZ treatment. These results suggest that PPAR-mediated processes may contribute to the mechanisms of action of NTZ therapy.

scholarly journals Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis

2020 ◽  
Vol 21 (23) ◽  
pp. 9329
Author(s):  
Elien Wouters ◽  
Elien Grajchen ◽  
Winde Jorissen ◽  
Tess Dierckx ◽  
Suzan Wetzels ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Foam Cell ◽  
Cell Formation ◽  
Autoimmune Disorder ◽  
Foam Cell Formation ◽  
Peroxisome Proliferator ◽  
Peripheral Blood Mononuclear ◽  
Peroxisome Proliferator Activated Receptors ◽  
Pparγ Expression

Macrophages play a crucial role during the pathogenesis of multiple sclerosis (MS), a neuroinflammatory autoimmune disorder of the central nervous system. Important regulators of the metabolic and inflammatory phenotype of macrophages are liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs). Previously, it has been reported that PPARγ expression is decreased in peripheral blood mononuclear cells of MS patients. The goal of the present study was to determine to what extent PPARγ, as well as the closely related nuclear receptors PPARα and β and LXRα and β, are differentially expressed in monocytes from MS patients and how this change in expression affects the function of monocyte-derived macrophages. We demonstrate that monocytes of relapsing-remitting MS patients display a marked decrease in PPARγ expression, while the expression of PPARα and LXRα/β is not altered. Interestingly, exposure of monocyte-derived macrophages from healthy donors to MS-associated proinflammatory cytokines mimicked this reduction in PPARγ expression. While a reduced PPARγ expression did not affect the inflammatory and phagocytic properties of myelin-loaded macrophages, it did impact myelin processing by increasing the intracellular cholesterol load of myelin-phagocytosing macrophages. Collectively, our findings indicate that an inflammation-induced reduction in PPARγ expression promotes myelin-induced foam cell formation in macrophages in MS.

scholarly journals The role of CXCR3 and its ligands expression in Brucellar spondylitis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Hu ◽  
Xiaoqian Shang ◽  
Liang Wang ◽  
Jiahui Fan ◽  
Yue Wang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Inflammatory Infiltration ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Inflammatory Damage ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

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.

scholarly journals Decreased PERP Expression on Peripheral Blood Mononuclear Cells from Patient with Rheumatoid Arthritis Negatively Correlates with Disease Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yanchun Du ◽  
Lin Deng ◽  
Yan Li ◽  
Lu Gan ◽  
Yantang Wang ◽  
...  
Keyword(s):  
Disease Activity ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Cell Types ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Cell Type Specific ◽  
Mrna Expression Levels

Background. PERP, p53 apoptosis effector related to PMP-22, is a p53-dependent apoptosis in diverse cell types and has cell type-specific roles in p53-mediated apoptosis. However, its role in PBMCs of RA patients has remained largely unclear.Objectives. The aim of this study was to detect the expression levels of PERP on PBMCs of RA patients and healthy controls and analyze the role of PERP in the pathogenesis of RA.Methods. The mRNA expression levels of PERP and IL-17 were detected by real-time PCR in PBMCs from patients with RA (n=40) and healthy controls (n=40). The correlations of PERP expression levels to IL-17 transcripts and disease activity parameters were analyzed.Results. The PERP and IL-17 expression levels in the PBMCs were significantly decreased and increased in comparison of which in healthy controls. The mRNA expression levels of PERP in PBMCs from patients with RA were negatively correlated with IL-17 and disease activity parameters DAS28, RF, CRP, and ESR rather than Anti-CCP and ANA.Conclusions. These results demonstrated that PERP might be involved in the pathogenesis and a potential therapeutic target of RA by regulating the expression of IL-17.

scholarly journals Elevated semaphorin 5A in patients with Hashimoto’s thyroiditis: a case–control study

2017 ◽  
Vol 6 (8) ◽  
pp. 659-666 ◽  
Author(s):  
Yongping Liu ◽  
Shuo Wang ◽  
Qingling Guo ◽  
Yongze Li ◽  
Jing Qin ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Hashimoto’S Thyroiditis ◽  
Mononuclear Cells ◽  
Elevated Serum ◽  
Hashimoto's Thyroiditis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Semaphorin 5A

Objective Hashimoto’s thyroiditis (HT) is characterized by elevated specific auto-antibodies, including TgAb and TPOAb. Increasing evidence has demonstrated the essential role of Th17 cells in HT. However, the underlying mechanism is still unclear. Semaphorin 5A (Sema 5A) is involved in several autoimmune diseases through the regulation of immune cells. The aim of the present study was to explore the role of Sema 5A in HT. Methods We measured serum Sema 5A levels in HT (n = 92) and healthy controls (n = 111) by enzyme-linked immunosorbent assay (ELISA). RNA levels of Sema 5A and their receptors (plexin-A1 and plexin-B3), as well as several cytokines (IFN-γ, IL-4 and IL-17), were detected by real-time polymerase chain reaction in peripheral blood mononuclear cells from 23 patients with HT and 31 controls. In addition, we investigated the relationship between serum Sema 5A and HT. Results Serum Sema 5A in HT increased significantly compared with healthy controls (P < 0.001). Moreover, serum Sema 5A levels were positively correlated with TgAb (r = 0.511, P < 0.001), TPOAb (r = 0.423, P < 0.001), TSH (r = 0.349, P < 0.001) and IL-17 mRNA expression (r = 0.442, P < 0.001). Increased Sema 5A RNA expression was observed (P = 0.041) in HT compared with controls. In receiver-operating characteristic (ROC) analysis, serum Sema 5A predicted HT with a sensitivity of 79.35% and specificity of 96.40%, and the area under the curve of the ROC curve was 0.836 (95% CI: 0.778–0.884, P < 0.001). Conclusions These data demonstrated elevated serum Sema 5A in HT patients for the first time. Serum Sema 5A levels were correlated with thyroid auto-antibodies and IL-17 mRNA expression. Sema 5A may be involved in immune response of HT patients.

scholarly journals Genetic Variation in CCL18 Gene Influences CCL18 Expression and Correlates with Survival in Idiopathic Pulmonary Fibrosis: Part A

2020 ◽  
Vol 9 (6) ◽  
pp. 1940 ◽  
Author(s):  
Ivo A. Wiertz ◽  
Sofia A. Moll ◽  
Benjamin Seeliger ◽  
Nicole P. Barlo ◽  
Joanne J. van der Vis ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Serum Levels ◽  
High Serum ◽  
Lung Fibroblasts ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Matrix Deposition

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease, characterized by fibroblast proliferation and extracellular matrix deposition. CC-chemokine ligand 18 (CCL18) upregulates the production of collagen by lung fibroblasts and is associated with mortality. This study was designed to evaluate the influence of single nucleotide polymorphisms (SNPs) in the CCL18 gene on CCL18 expression and survival in IPF. Serum CCL18 levels and four SNPs in the CCL18 gene were analyzed in 77 Dutch IPF patients and 349 healthy controls (HCs). CCL18 mRNA expression was analyzed in peripheral blood mononuclear cells (PBMCs) from 18 healthy subjects. Survival analysis was conducted, dependent on CCL18-levels and -genotypes and validated in two German IPF cohorts (Part B). IPF patients demonstrated significantly higher serum CCL18 levels than the healthy controls (p < 0.001). Both in IPF patients and HCs, serum CCL18 levels were influenced by rs2015086 C > T genotype, with the highest CCL18-levels with the presence of the C-allele. Constitutive CCL18 mRNA-expression in PBMCs was significantly increased with the C-allele and correlated with serum CCL18-levels. In IPF, high serum levels correlated with decreased survival (p = 0.02). Survival was worse with the CT-genotype compared to the TT genotype (p = 0.01). Concluding, genetic variability in the CCL18-gene accounts for differences in CCL18 mRNA-expression and serum-levels and influences survival in IPF.

scholarly journals Genetic Association and Altered Gene Expression of CYBB in Multiple Sclerosis Patients

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 117 ◽  
Author(s):  
Giulia Cardamone ◽  
Elvezia Paraboschi ◽  
Giulia Soldà ◽  
Stefano Duga ◽  
Janna Saarela ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nucleotide Polymorphisms ◽  
Autoimmune Encephalomyelitis ◽  
Peripheral Blood Mononuclear ◽  
Disease Predisposition ◽  
Altered Gene ◽  
Functional Relevance ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic neurological disorder characterized by inflammation, demyelination, and axonal damage. Increased levels of reactive oxygen species (ROS), produced by macrophages and leading to oxidative stress, have been implicated as mediators of demyelination and axonal injury in both MS and experimental autoimmune encephalomyelitis, the murine model of the disease. On the other hand, reduced ROS levels can increase susceptibility to autoimmunity. In this work, we screened for association with MS 11 single nucleotide polymorphisms (SNPs) and two microsatellite markers in the five genes (NCF1, NCF2, NCF4, CYBA, and CYBB) of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) system, the enzymatic pathway producing ROS in the brain and neural tissues, in 347 Finnish patients with MS and 714 unaffected family members. This analysis showed suggestive association signals for NCF1 and CYBB (lowest p = 0.038 and p = 0.013, respectively). Functional relevance for disease predisposition was further supported for the CYBB gene, by microarray analysis in CD4+/− mononuclear cells of 21 individuals from five Finnish multiplex MS families, as well as by real-time RT-PCRs performed on RNA extracted from peripheral blood mononuclear cells of an Italian replication cohort of 21 MS cases and 21 controls. Our results showed a sex-specific differential expression of CYBB, suggesting that this gene, and more in general the NOX2 system, deserve to be further investigated for their possible role in MS.

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