An investigation of the inflammatory cytokine and chemokine network in systemic sclerosis

2011 ◽  
Vol 70 (6) ◽  
pp. 1115-1121 ◽  
Author(s):  
Veronica Codullo ◽  
Helen M Baldwin ◽  
Mark D Singh ◽  
Alasdair R Fraser ◽  
Catherine Wilson ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mononuclear Cells ◽  
Platelet Rich Plasma ◽  
Critical Role ◽  
Serum Levels ◽  
Pcr Analysis ◽  
Peripheral Blood Mononuclear ◽  
Matrix Deposition ◽  
Disease Subtype ◽  
Inflammatory Chemokines

ObjectivesSystemic sclerosis (SSc) is characterised by vasculopathy, an aberrantly activated immune system and excessive extracellular matrix deposition. Inflammatory chemokines control migration of cells to sites of tissue damage; their removal from inflamed sites is essential for resolution of the inflammatory response. The atypical chemokine receptor D6 has a critical role in this physiological balance. To explore potential deregulation of this system in SSc, inflammatory chemokine and D6 expression were compared with that in healthy controls (HC).MethodsSerum levels of inflammatory mediators were assessed by luminex analysis. Peripheral blood mononuclear cells (PBMCs) were used in molecular and immunocytochemical analysis. Platelet-rich plasma was collected and assessed by western blotting for D6 expression levels. Sex-matched HC were used for comparison.Results72 patients with SSc and 30 HC were enrolled in the study. The chemokines MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4 and IL-8/CXCL8 were significantly increased in patients with SSc, regardless of disease subtype and phase. Quantitative PCR analysis revealed a significant 10-fold upregulation of D6 transcripts in patients with SSc compared with controls, and this was paralleled by increased D6 protein expression in the PBMCs of patients with SSc. Platelet lysates also showed strong D6 expression in patients with SSc but not in controls. Importantly, high levels of D6 expression correlated with reduced levels of its ligands in serum.ConclusionsInflammatory chemokines and the regulatory receptor D6 are significantly upregulated in SSc and high D6 levels are associated with lower systemic chemokine levels, indicating that some patients control systemic chemokine levels using D6. These results suggest that chemokines may represent a therapeutic target in SSc.

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 Increased Level of Caspase-1 in the Serum of Relapsing-remitting Multiple Sclerosis (RRMS) Patients

2020 ◽  
Author(s):  
Masoumeh Beheshti ◽  
Zahra Salehi ◽  
Roya Abolfazli ◽  
Hedayatolah Shirzad ◽  
Maryam Izad
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Serum Levels ◽  
Peripheral Blood Mononuclear ◽  
Caspase 1 ◽  
Significant Difference ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
And Gender

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, in which proinflammatory cytokines play a critical role in the pathogenic formation of lesions. Caspase-1 is a cysteine protease that proteolytically cleaves precursors of interleukin (IL)-18 and IL-1β and turns them into their active forms. These inflammatory cytokines play an important role in the development of MS. The aim of the present study was the investigation of caspase-1 and its downstream products, IL-18 and IL-1β, in relapsing-remitting MS (RRMS) patients. In this study, we used an ELISA assay to measure serum and cellular caspase-1 and serum levels of IL-18 and IL-1β in RRMS patients in the relapse phase (n=23) and healthy age-and gender-matched controls (n=19). We observed that the caspase-1 level was significantly increased in the serum of MS patients compared to the healthy controls (p=0.03). Although caspase-1 concentration in the lysate of peripheral blood mononuclear cells (PBMCs) was higher than serum among patients and controls (p<0.001), no significant difference was found in cellular levels of caspase-1 between the two groups. There was no significant difference in serum levels of  IL-18 and IL-1β between patients and controls. In this study, we found an elevation of extracellular caspase-1, as a reflection of its intracellular level, in the serum of RRMS patients during the relapse phase. Therefore, it suggests being a suitable peripheral biomarker of disease activity in multiple sclerosis.

Inversely Association of the Aiolos Transcription Factor with Clinical Progression in Chronic Lymphocytic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2069-2069
Author(s):  
Holger Nückel ◽  
Ulrich H Frey ◽  
Ludger Sellmann ◽  
Crista H Collins ◽  
Ulrich Duehrsen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
B Cells ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Lymphocytic Leukemia ◽  
Pcr Analysis ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Cd38 Expression ◽  
Important Regulator

Abstract Introduction: Aiolos encode a hemopoietic-specific zinc-finger transcription factor that is an important regulator of lymphocyte differentiation and plays a critical role in regulating B-cell development. RT-PCR analysis of the Aiolos gene expression revealed 16 Aiolos splicing variants, which have been named according to the exons missing from the full-length isoform. Recent data suggest that over 80% of expressed Aiolos in normal as well as in malignant B-cells is of the hAio1 type. Therefore, we investigated Aiolos mRNA expression (hAio1 type) in a large cohort with 155 patients along with the most commonly used biological markers in order to assess its role in risk prediction in B-CLL. Methods and Results: The total amount of Aiolos transcripts in B-cells of 155 CLL patients using normal peripheral blood mononuclear cells represented a continuum ranging from 2.5- to 37-fold upregulation compared to that of normal B-cells, with a median of 20- fold upregulation. Moreover, Aiolos expression in B-CLL was significantly upregulated compared to cells of AML (113-fold; p&lt;0.0001), ALL (14-fold; p=0.0024), CML (154- fold; p&lt;0.0001), multiple myeloma (38-fold; p=0.0018) or NHL (16-fold; p&lt;0.0001) suggesting that this Aiolos transcript is highly expressed specifically in B-CLL cells Patients with high Aiolos expression (according to ROC-analysis) had a significantly longer treatment-free survival (TFS) and overall survival (OS) than patients with low Aiolos expression (median TFS: 119 versus 45 months, p=0.005; median OS: 321 versus 244 months, p=0.0065). Evaluation of several disease characteristics in association with the Aiolos expression status of the patients’ B-CLL cells showed no significant differences for ZAP-70 expression (p=0.28), CD38 expression (p=0.067), IgVH status (p=0.49) and Binet stage (p=0.13) suggesting no correlation of Aiolos expression with these already established adverse prognostic factors. In multivariate analysis low Aiolos expression was an independent prognostic factor with significance for trend (hazard ratio 1.413; p=0.069). Sequential analyses in a subset of 10 CLL patients revealed that Aiolos expression was relatively stable over time in the majority of patients. Conclusions: Here we demonstrate for the first time that the level of Aiolos expression is correlated with prognosis in B-CLL. The exact causes and consequences of this upregulation on the survival of CLL B-cells and the demonstrated better prognosis have yet to be determined. However, Aiolos may function as a tumor suppressor by controlling the cell cycle and DNA replication.

scholarly journals Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Andréa Tavares Dantas ◽  
Sayonara Maria Calado Gonçalves ◽  
Anderson Rodrigues de Almeida ◽  
Rafaela Silva Guimarães Gonçalves ◽  
Maria Clara Pinheiro Duarte Sampaio ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Vascular Involvement ◽  
Digital Ulcers ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear ◽  
Pbmc Culture ◽  
Significant Difference ◽  
Skin Biopsies

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

scholarly journals POS0430 EXPRESSION AND CLINICAL SIGNIFICANCE OF AUTOPHAGY-RELATED GENES IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 443.2-443
Author(s):  
Y. F. Qing ◽  
J. Zheng ◽  
S. B. Wang ◽  
F. Dai ◽  
Y. Jiang ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Significance ◽  
Normal Control ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Beclin 1 ◽  
Peripheral Blood Mononuclear ◽  
Mesenchymal Transition ◽  
Blood Mononuclear Cells

Background:Growing evidences have demonstrated that autophagy is a powerful regulators in the pathogenesis of fibrosis and autoimmune diseases. Autophagy abnormalities in SSc involve abnormal autophagy-related protein and autophagy-related gene polymorphism[1-2], however there is a few reports on the expression and clinical significance of autophagy-related genes.Objectives:To investigate the expression and clinical significance of autophagy-related genes LC-3 mRNA, Becline-1 mRNA, Agt-3 mRNA, Agt-5 mRNA, Agt-12 mRNA and Agt-16L1 mRNA in peripheral blood mononuclear cells (PBMC) of systemic sclerosis (SSc).Methods:51 cases of SSc and 60 cases of normal control were received from the Affiliated Hospital of North Sichuan Medical College, and autophagy-related genes were detected by RT-PCR. SPSS19.0 statistical software was used to compare the expression of autophagy-related genes between groups and analyze the relationship between autophagy-related genes and clinical data, P<0.05 was considered statistically significantResults:LC-3, Becline-1, and Agt-3 were highly expressed in SSc compared with normal control [LC-3: 0.78(0.60) ×10-3 vs. 0.52(0.54) ×10-3; Beclin-1: 6.68(3.56)×10-3 vs. 5.22(3.54)×10-3; Agt-3: 17.58(12.33)×10-3 vs. 11.00(4.56)×10-3, P<0.05], however Agt-5, Agt-12 and Agt-16L1 of autophagy-related genes were not statistically significant [AGT-5: 6.67(3.58) ×10-3 vs. 6.67(2.64) ×10-3; AGT-12: 8.64(5.56)×10-3 vs. 8.57(4.66)×10-3; Agt-16L1: 2.69(2.19)×10-3 vs. 2.52(2.26)×10-3] (Figure 1). Beclin-1 and Agt-5 high expressed in SSc with the positive of anti-SSA/Ro antibody. LC-3 was positively correlated with Age(r=0.662) and ESR(r=0.355) (all P<0.05).Conclusion:Autophagy-related genes were increased in PBMC of SSc, and were correlated with Age, ESR and autoantibody, suggested that autophagy is a key feature in the pathogenesis of systemic sclerosis.Figure 1.The relative expression of autophagy-related genesReferences:[1]LIU C, ZHOU X, LU J, et al. Autophagy mediates 2-methoxyestradiol-inhibited scleroderma collagen synthesis and endothelial-to-mesenchymal transition induced by hypoxia[J]. Rheumatology, 2019;58(11):1966–1975.[2]Mayes M D, Bossini-Castillo L, Gorlova O, et al. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis[J]. The American Journal of Human Genetics, 2014,94(1):47-61.DOI:10.1016/j.ajhg.2013.12.002.Disclosure of Interests:None declared

Increased Serum Interleukin 22 in Patients with Rheumatoid Arthritis and Correlation with Disease Activity

2012 ◽  
Vol 39 (7) ◽  
pp. 1320-1325 ◽  
Author(s):  
LAURINDO FERREIRA da ROCHA ◽  
ÂNGELA LUZIA BRANCO PINTO DUARTE ◽  
ANDRÉA TAVARES DANTAS ◽  
HENRIQUE ATAÍDE MARIZ ◽  
IVAN da ROCHA PITTA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Mononuclear Cells ◽  
Activity Index ◽  
Elevated Serum ◽  
Serum Levels ◽  
Peripheral Blood Mononuclear ◽  
Additional Tool ◽  
Bone Erosions ◽  
Interleukin 22

Objective.To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).Methods.IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulatedin vitrowith phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.Results.IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).Conclusion.IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.

scholarly journals The immunoregulatory function of peripheral blood CD71+ erythroid cells in systemic-onset juvenile idiopathic arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hikaru Kanemasa ◽  
Masataka Ishimura ◽  
Katsuhide Eguchi ◽  
Tamami Tanaka ◽  
Etsuro Nanishi ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Active Phase ◽  
Serum Levels ◽  
Cell Interaction ◽  
Erythroid Cells ◽  
Peripheral Blood Mononuclear ◽  
Systemic Onset

AbstractCD71+ erythroid cells (CECs) are recognized to have an immunoregulatory function via direct cell–cell interaction and soluble mediators. Circulating CECs appear in newborns or patients with hemolytic and cardiopulmonary disorders. To assess the biological role of CECs in systemic inflammation, we studied the gene expression and function in systemic-onset juvenile idiopathic arthritis (SoJIA). Peripheral blood mononuclear cells of SoJIA patients expressed upregulated erythropoiesis-related genes. It represented the largest expansion of CECs during active phase SoJIA among other inflammatory diseases. Despite the opposing roles of erythropoietin and hepcidin in erythropoiesis, both serum levels were in concert with the amounts of SoJIA-driven CECs. Circulating CECs counts in inflammatory diseases were positively correlated with the levels of C-reactive protein, IL-6, IL-18, or soluble TNF receptors. Co-culture with active SoJIA-driven CECs suppressed secretions of IL-1β, IL-6, and IL-8 from healthy donor monocytes. The top upregulated gene in SoJIA-driven CECs was ARG2 compared with CECs from cord blood controls, although cytokine production from monocytes was suppressed by co-culture, even with an arginase inhibitor. CECs are driven to the periphery during the acute phase of SoJIA at higher levels than other inflammatory diseases. Circulating CECs may control excessive inflammation via the immunoregulatory pathways, partly involving arginase-2.

Sign in / Sign up

Export Citation Format

Share Document