Higher Circulating Levels of Chemokine CCL20 in Patients with Multiple Sclerosis: Evaluation of the Influences of Chemokine Gene Polymorphism, Gender, Treatment and Disease Pattern

Jafarzadeh, Abdollah; Bagherzadeh, S.; Ebrahimi, Hossein Ali; Hajghani, Hossain; Bazrafshani, Mohammadreza; Khosravimashizi, Arezu; Nemati, Maryam; Gadari, Faranak; Sabahi, Abdolreza; Iranmanesh, Farhad; Mohammadi, Mohammad Mahdi; Daneshvar, Hamid

doi:10.1007/s12031-013-0214-2

Cited by 39 publications

(25 citation statements)

References 22 publications

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“…The accompanying polymorphism of the gene in MS patients in Egypt shows an increased risk of MS rather than an individual locus [29]. Another study from Iran showed that the rs6749704 polymorphism is associated with the SPMS model [45].…”

Section: Ccl20/ccr6mentioning

confidence: 99%

The role of chemokines and chemokine receptors in multiple sclerosis

Cui

Chu

Chen

2020

International Immunopharmacology

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Multiple sclerosis (MS) is a chronic inflammatory disease that is characterized by leukocyte infiltration and subsequent axonal damage, demyelinating inflammation, and formation of sclerosing plaques in brain tissue. The results of various studies in patients indicate that autoimmunity and inflammation make an important impact on the pathogenesis of MS. Chemokines are key mediators of inflammation development and cell migration, mediating various immune cell responses, including chemotaxis and immune activation, and are important in immunity and inflammation, therefore we focus on chemokines and their receptors in multiple sclerosis. In this article, we summarize the study of the role of prominent chemokines and their receptors in MS patients and MS animal modelsand discuss their potential significance in inflammatory injury and repair of MS. We have also summarized the progress in the treatment of multiple sclerosis antagonists in recent years with chemokine receptors as targets.

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Section: Ccl20/ccr6mentioning

confidence: 99%

The role of chemokines and chemokine receptors in multiple sclerosis

Cui

Chu

Chen

2020

International Immunopharmacology

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“…The role of Th2 cells, which secrete high levels of IL-4, IL-5, and IL-13, remains controversial (Raphael et al 2015). We have previously observed the elevated concentrations of a Th17-related chemokine (CCL20), diminished levels of a Th2/Treg-related chemokine (CCL22), and unchanged levels of a Treg-related cytokine in patients with MS (Jafarzadeh et al 2014a;Jafarzadeh et al 2014b;Jafarzadeh et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Altered Expression of Specific Transcription Factors of Th17 (RORγt, RORα) and Treg Lymphocytes (FOXP3) by Peripheral Blood Mononuclear Cells from Patients with Multiple Sclerosis

et al. 2016

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The imbalance in Th17/Treg cell-related responses plays an important role in the pathogenesis of multiple sclerosis (MS). The development of Th17- and Treg cells is regulated by specific transcription factors-RORγt and RORα-and FOXP3, respectively. The aim was to determine the expression of RORγt, RORα, and FOXP3 in peripheral blood mononuclear cells (PBMCs) from MS patients following in vitro stimulation. The PBMCs from 22 MS patients and 20 healthy subjects were cultured in the presence of 10 μg/ml MOG, 10 μg/ml PHA, or without stimulation. The PBMCs were incubated at 37 °C for 24 h, and then the messenger RNA (mRNA) expression of RORγt, RORα, and FOXP3 was determined by real-time PCR. The expression of RORγt and RORα was increased in non-stimulated, MOG-stimulated, and PHA-stimulated PBMCs from MS patients in comparison with same cultures from the healthy group (P < 0.01, P < 0.01, and P < 0.02 for RORγt; P < 0.001, P < 0.001, and P < 0.05, for RORα, respectively). The FOXP3 expression in non-stimulated PBMCs from MS patients was significantly lower than that in equal culture from healthy subjects (P < 0.05). There were no significant differences between healthy subjects and MS patients regarding the expression of FOXP3 mRNA by MOG-stimulated and PHA-stimulated PBMCs. These results showed an imbalance in Th17/Treg cells at transcription factor levels with a deviation toward Th17 cell in MS. The correction of Th17/Treg balance at transcription levels should be considered to design novel therapeutic strategies for MS treatment.

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“…Since its initial cloning, CCL20 has been implicated in a diverse set of inflammatory conditions, including rheumatoid arthritis [31], multiple sclerosis [32] and islet viral infection [33]. Indeed, CCL20 is able to chemoattract both adaptive and innate immune cells, including CD4 + and CD8 + T-cells [34, 35], dendritic cells [36], B-lymphocytes [37, 38] and natural killer (NK) cells [39].…”

Section: 1 Introductionmentioning

confidence: 99%

CCL20 is elevated during obesity and differentially regulated by NF-κB subunits in pancreatic β-cells

Burke

Karlstad

Regal

et al. 2015

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Enhanced leukocytic infiltration into pancreatic islets contributes to inflammation-based diminutions in functional β-cell mass. Insulitis (aka islet inflammation), which can be present in both T1DM and T2DM, is one factor influencing pancreatic β-cell death and dysfunction. IL-1β, an inflammatory mediator in both T1DM and T2DM, acutely (within 1h) induced expression of the CCL20 gene in rat and human islets and clonal β-cell lines. Transcriptional induction of CCL20 required the p65 subunit of NF-κB to replace the p50 subunit at two functional κB sites within the CCL20 proximal gene promoter. The NF-κB p50 subunit prevents CCL20 gene expression during unstimulated conditions and overexpression of p50 reduces CCL20, but enhances cyclooxygenase-2 (COX-2), transcript accumulation after exposure to IL-1β. We also identified differential recruitment of specific co-activator molecules to the CCL20 gene promoter, when compared with the CCL2 and COX2 genes, revealing distinct transcriptional requirements for individual NF-κB responsive genes. Moreover, IL-1β, TNF-α and IFN-γ individually increased the expression of CCR6, the receptor for CCL20, on the surface of human neutrophils. We further found that the chemokine CCL20 is elevated in serum from both genetically obese db/db mice and in C57BL6/J mice fed a high-fat diet. Taken together, these results are consistent with a possible activation of the CCL20-CCR6 axis in diseases with inflammatory components. Thus, interfering with this signaling pathway, either at the level of NF-κB-mediated chemokine production, or downstream receptor activation, could be a potential therapeutic target to offset inflammation-associated tissue dysfunction in obesity and diabetes.

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Higher Circulating Levels of Chemokine CCL20 in Patients with Multiple Sclerosis: Evaluation of the Influences of Chemokine Gene Polymorphism, Gender, Treatment and Disease Pattern

Cited by 39 publications

References 22 publications

The role of chemokines and chemokine receptors in multiple sclerosis

The role of chemokines and chemokine receptors in multiple sclerosis

Altered Expression of Specific Transcription Factors of Th17 (RORγt, RORα) and Treg Lymphocytes (FOXP3) by Peripheral Blood Mononuclear Cells from Patients with Multiple Sclerosis

CCL20 is elevated during obesity and differentially regulated by NF-κB subunits in pancreatic β-cells

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