scholarly journals The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4968
Author(s):  
Samuel García-Arellano ◽  
Luis Alexis Hernández-Palma ◽  
Sergio Cerpa-Cruz ◽  
Gabriela Athziri Sánchez-Zuno ◽  
Melva Guadalupe Herrera-Godina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Joint Destruction ◽  
Study Groups ◽  
Joint Disease ◽  
The Novel ◽  
Peripheral Blood Mononuclear ◽  
Cytokine Dysregulation ◽  
New Evidence

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.

scholarly journals Arthritis and the role of endogenous glucocorticoids

Bone Research ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Eugenie Macfarlane ◽  
Markus J. Seibel ◽  
Hong Zhou
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Current Evidence ◽  
Inflammatory Microenvironment ◽  
Glucocorticoid Signaling ◽  
Anti Inflammatory ◽  
Fibroblast Like Synoviocytes

Abstract Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.

scholarly journals TO008COMPARATIVE TRANSCRIPTOME AND CO-EXPRESSION NETWORK ANALYSIS REVEALED A POTENTIAL ROLE OF C1QB AND INTERFERON TYPE 1 PATHWAY IN CIRCULATING IMMUNE CELLS OF KIDNEY TRANSPLANTS PATIENTS WITH CHRONIC ANTIBODY MEDIATED REJECTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gloria Santoro ◽  
Simona Granata ◽  
Paola Pontrelli ◽  
Mattia Rossi ◽  
Giovanni Gambaro ◽  
...  
Keyword(s):  
Network Analysis ◽  
Mononuclear Cells ◽  
Pathological Condition ◽  
Inflammatory Cells ◽  
Study Groups ◽  
Molecular Diagnostic ◽  
Peripheral Blood Mononuclear ◽  
Antibody Mediated Rejection

Abstract Background and Aims Chronic antibody-mediated rejection (CAMR) is a multifactorial pathological condition that can affect more that 40-50% of kidney allografts. Its clinical evolution is often silent, and this can delay its diagnosis. Although many advances in understanding the biological mechanisms underlying its onset/development, at the moment, no reliable non-invasive diagnostic biomarkers are available in clinic. Method We enrolled 29 patients with biopsy-proven CAMR, 29 stable transplant recipients (controls). Subsequently, the microarray profile of mRNA isolated from peripheral blood mononuclear cells (PBMCs) from 10 randomly selected CAMR patients and 10 controls was evaluated by Agilent technology. For the bioinformatics analysis we employed several statistical algorithms (including ANOVA and Kruskal-Wallis tests adjusted for multiple-tests) and a Weighted Gene Correlation Network Analysis (WGCNA) to select genes biologically associated in co-expressed networks. Results 935 genes resulted differentially expressed between the two study groups, demonstrating the large biological impact of this pathological condition on circulating immune-inflammatory cells. After WGCNA co-expression analysis, a group of genes (enclosed in a single co-expression module, 13 genes) resulted highly discriminating CAMR versus controls (p&lt;.5.2 e-7, FDR&lt;1%). This module included: Interferon-induced transmembrane proteins (IFITM) 2, 3, 4, confirming previous results by our group. However, the top discriminative gene was C1QB (Complement component 1, q subcomponent, B chain, p &lt;000.1), a key element involved in the classical complement pathway. ELISA confirmed the microarray results on the entire patients’ cohort. Conclusion Our study confirmed the role of the type 1 interferon pathway in CAMR and underlined its capability to promote C1QB expression. These effects could contribute to better define the role of innate immunity in CAMR. Finally, C1QB, if validated in a large cohort of patients, could represent a new valuable molecular diagnostic biomarker for this complication.

The Effects of Hydroalcoholic Extract from Alhagi on Matrix Metalloproteinase- 9 Production in Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis

2020 ◽  
Vol 10 (4) ◽  
pp. 440-445
Author(s):  
Mahbouba Ahmadi ◽  
Reyhane Ebrahimi ◽  
Mohammad Ansari ◽  
Masoumeh Akhlaghi ◽  
Mahdi Mahmoudi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinase ◽  
Peripheral Blood Mononuclear Cells ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Joint Destruction ◽  
Peripheral Blood Mononuclear ◽  
Hydroalcoholic Extract ◽  
Blood Mononuclear Cells ◽  
Metalloproteinase 9

Background: The up-regulation of matrix metalloproteinase 9 (MMP-9) along with the imbalanced ratio of MMP-9 to tissue inhibitor of metalloproteinase 1 (TIMP-1) is important in the pathogenesis of Rheumatoid Arthritis (RA). Here, we investigated whether hydroalcoholic extract from the root of Alhagi camelorum Fisch can affect the levels of MMP-9 and TIMP-1 in peripheral blood mononuclear cells (PBMCs) of RA patients. Objective: In the current study, we suggest that Alhagi may have an inhibitory effect on MMP-9 production, which is mainly responsible for joint destruction in RA. In addition, we would like to stress that our findings, along with others, can provide the basis for future studies, which might help in determining the role of chemical ingredients of Alhagi as therapeutic targets for RA treatment. Methods: PBMCs were isolated from 12 RA patients and 12 healthy subjects and treated with two concentrations of Alhagi extract (100 and 500 μg/ml) for 24 h. MMP-9 gene expression and protein production, TIMP-1 levels and nitric oxide (NO) production were evaluated using standard methods. Results: Alhagi (500 μg/ml) caused a significant reduction in the expression and activity of MMP-9 in PBMCs from healthy (p=0.003 for both of them) and patient (p= 0.05 and p=0.02 respectively) subjects. Moreover, Alhagi (100 μg/ml) decreased MMP-9 production in the healthy subjects’ group (p=0.02). Conclusion: The present study reveals the inhibitory effects of Alhagi on the production of MMP-9 as the main responsible cause of joint destruction in RA.

Effects of the Neuropeptide, Substance P, on Lymphocyte Proliferation in Rheumatoid Arthritis

1995 ◽  
Vol 23 (6) ◽  
pp. 431-438 ◽  
Author(s):  
M Jovas ◽  
L A Pinto ◽  
J A Pereira da Silva ◽  
R M M Victorino
Keyword(s):  
Rheumatoid Arthritis ◽  
Substance P ◽  
Lymphocyte Proliferation ◽  
Mononuclear Cells ◽  
Thymidine Incorporation ◽  
Lymphocyte Activation ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Dose Dependent

There is evidence supporting the involvement of the neuropeptide, substance P, in the pathogenesis of rheumatoid arthritis. In view of the suggested role of T-cells in this disease, we have investigated the effects of substance P on mitogen-induced lymphocyte proliferation in rheumatoid arthritis patients. The peripheral blood mononuclear cells from 20 patients with rheumatoid arthritis and 25 controls were cultured in the presence or absence of substance P (10−-10 M to 10−-6 M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days of culture the proliferative responses were determined by measuring [3H]thymidine incorporation into the cells. Substance P enhanced, in a dose-dependent manner, the lymphocyte proliferative responses both in rheumatoid arthritis patients and in controls. Although there was a trend towards a greater enhancing effect in the rheumatoid arthritis patients, this was not statistically significant. Some individual patients with rheumatoid arthritis showed enhancements of lymphocyte proliferation with substance P that were clearly outside the range seen in healthy controls. The possibility that substance P has a role in the pathogenesis of rheumatoid arthritis through the up-regulation of lymphocyte activation should be considered in further studies of the immunomodulatory properties of substance P in arthritis.

Immunoregulatory Role of Interleukin-37 in Rheumatoid Arthritis; Relation to Disease Activity and Joint Destruction

2018 ◽  
Vol 86 (September) ◽  
pp. 3341-3348
Author(s):  
DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽  
MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Destruction

The Role of Synovial Fibroblasts in Mediating Joint Destruction in Rheumatoid Arthritis

2005 ◽  
Vol 11 (5) ◽  
pp. 563-568 ◽  
Author(s):  
Ingmar Meinecke ◽  
Edita Rutkauskaite ◽  
Steffen Gay ◽  
Thomas Pap
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Synovial Fibroblasts

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Inflammatory Processes ◽  
Related Proteins ◽  
Local Stimulation ◽  
Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

scholarly journals Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321731
Author(s):  
Dominik Aschenbrenner ◽  
Maria Quaranta ◽  
Soumya Banerjee ◽  
Nicholas Ilott ◽  
Joanneke Jansen ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Personalised Medicine ◽  
Mononuclear Phagocytes ◽  
Cytokine Network ◽  
Peripheral Blood Mononuclear ◽  
Transcriptional Signature ◽  
Inflammatory Monocytes ◽  
Transcriptomic Signature ◽  
Inflammatory Bowel

ObjectiveDysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.DesignWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.ResultsWe characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.ConclusionOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.

scholarly journals OP0033 REGULATORY T CELL CD39 EXPRESSION AS A PREDICTOR OF EARLY REMISSION-INDUCTION WITH METHOTREXATE IN NEW-ONSET RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 18.2-18
Author(s):  
P. Brown ◽  
A. Anderson ◽  
B. Hargreaves ◽  
A. Morgan ◽  
J. D. Isaacs ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Disease Modifying Therapy ◽  
Blood Mononuclear Cells ◽  
Treatment Naïve ◽  
Disease Modifying ◽  
Pre Treatment

Background:The long term outcomes for patients with rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate remains the key first line disease modifying therapy for the majority of patients, with 40% achieving an ACR50 on monotherapy(1). There are at present no effective biomarkers to predict treatment response, preventing effective personalisation of therapy. A putative mechanism of action of methotrexate, the potentiation of anti-inflammatory adenosine signalling, may inform biomarker discovery. By antagonism of the ATIC enzyme in the purine synthesis pathway, methotrexate has been proposed to increase the release of adenosine moieties from cells, which exert an anti-inflammatory effect through interaction with ADORA2 receptors(2). Lower expression of CD39 (a cell surface 5-’ectonucleotidase required for the first step in the conversion of ATP to adenosine) on circulating regulatory T-Lymphocytes (Tregs) was previously identified in patients already established on methotrexate who were not responding (DAS28 >4.0 vs <3.0)(3). We therefore hypothesised that pre-treatment CD39 expression on these cells may have clinical utility as a predictor of early methotrexate efficacy.Objectives:To characterise CD39 expression in peripheral blood mononuclear cells in RA patients naïve to disease modifying therapy commencing methotrexate, and relate this expression to 4 variable DAS28CRP remission (<2.6) at 6 months.Methods:68 treatment naïve early RA patients starting methotrexate were recruited from the Newcastle Early Arthritis Clinic and followed up for 6 months. Serial blood samples were taken before and during methotrexate therapy with peripheral blood mononuclear cells isolated by density centrifugation. Expression of CD39 by major immune subsets (CD4+ and CD8+ T-cells, B-lymphocytes, natural killer cells and monocytes) was determined by flow cytometry. The statistical analysis used was binomial logistic regression with baseline DAS28CRP used as a covariate due to the significant association of baseline disease activity with treatment response.Results:Higher pre-treatment CD39 expression was observed in circulating CD4+ T-cells of patients who subsequently achieved clinical remission at 6 months versus those who did not (median fluorescence 4854.0 vs 3324.2; p = 0.0108; Figure 1-A). This CD39 expression pattern was primarily accounted for by the CD4+CD25 high sub-population (median fluorescence 9804.7 vs 6455.5; p = 0.0065; Figure 1-B). These CD25 high cells were observed to have higher FoxP3 and lower CD127 expression than their CD39 negative counterparts, indicating a Treg phenotype. No significant associations were observed with any other circulating subset. A ROC curve demonstrates the discriminative utility of differential CD39 expression in the CD4+CD25 high population for the prediction of DAS28CRP remission in this cohort, showing greater specificity than sensitivity for remission prediction(AUC: 0.725; 95% CI: 0.53 - 0.92; Figure 1-C). Longitudinally, no significant induction or suppression of the CD39 marker was observed amongst patients who did or did not achieve remission over the 6 months follow-up period.Figure 1.Six month DAS28CRP remission versus pre-treatment median fluorescence of CD39 expression on CD4+ T-cells (A); CD25 High expressing CD4+ T-cells (B); and ROC curve of predictive utility of pre-treatment CD39 expression on CD25 High CD4+ T-cells (C).Conclusion:These findings support the potential role of CD39 in the mechanism of methotrexate response. Expression of CD39 on circulating Tregs in treatment-naïve RA patients may have particular value in identifying early RA patients likely to respond to methotrexate, and hence add value to evolving multi-parameter discriminatory algorithms.References:[1]Hazlewood GS, et al. BMJ. 2016 21;353:i1777[2]Brown PM, et al. Nat Rev Rheumatol. 2016;12(12):731-742[3]Peres RS, et al. Proc Natl Acad Sci U S A. 2015;112(8):2509-2514Disclosure of Interests:None declared

Sign in / Sign up

Export Citation Format

Share Document