Dataset Information

Secretion of pro-inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast-like synoviocytes in juvenile idiopathic arthritis.

ABSTRACT:

Purpose

The goal is to investigate the specific contribution of fibroblast-like synoviocytes (FLS) to the inflammatory milieu of the synovium in juvenile idiopathic arthritis (JIA) through detection of secreted proteins.

Experimental design

Expression of 89 cytokines and chemokines is determined on unprocessed synovial fluid from controls and JIA patients using antibody arrays. Supernatants from pure cell cultures of FLS grown from synovial fluids or tissues from JIA and controls are also examined for protein expression. Ingenuity Pathway Analysis (IPA) is revealed top pathways and upstream regulators of significant proteins.

Results

Protein studies is revealed that JIA FLS release pro-inflammatory cytokines and chemokines, including IL-4, IL-6, IL-17, CXCL1, and CXCL6, and lose expression of important regulator signals, such as IL-10 and TIMP2. Of the 84 proteins differentially expressed between controls and JIA in the synovial fluid, 1/3 (29 proteins) are differentially expressed in the cell culture supernatants of JIA and control FLS. ELISA of cell culture supernatants and synovial fluid confirmed seven key proteins.

Conclusion and clinical relevance

JIA FLS are central to perpetuation of inflammation in JIA, including trafficking of inflammatory cells and effects on the extracellular matrix. These cells express key disease-specific chemokines that, with further refinement, may allow us to tailor therapy appropriately.

SUBMITTER: Brescia AC

PROVIDER: S-EPMC6084365 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Secretion of pro-inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast-like synoviocytes in juvenile idiopathic arthritis.

Brescia AnneMarie C AC Simonds Megan M MM Sullivan Kathleen E KE Rose Carlos D CD

Proteomics. Clinical applications 20170117 5-6

<h4>Purpose</h4>The goal is to investigate the specific contribution of fibroblast-like synoviocytes (FLS) to the inflammatory milieu of the synovium in juvenile idiopathic arthritis (JIA) through detection of secreted proteins.<h4>Experimental design</h4>Expression of 89 cytokines and chemokines is determined on unprocessed synovial fluid from controls and JIA patients using antibody arrays. Supernatants from pure cell cultures of FLS grown from synovial fluids or tissues from JIA and controls ...[more]

PMID: 28012239

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Project description:Adiponectin is an adipokine with a modulatory role in metabolism and exerting both anti- and pro-inflammatory effects. Levels of adiponectin are increased in serum and synovial fluid from patients with rheumatoid arthritis (RA). Adiponectin is able to stimulate the production of different pro-inflammatory factors from peripheral blood mononuclear cells (PBMCs) and fibroblast-like synoviocytes (FLS) from subjects with established RA. As increased circulating adiponectin levels are a risk factor for future development of RA in subjects with obesity, we hypothesize that adiponectin is implicated in the development of RA at an early stage by initiating the pro-inflammatory processes associated with the disease pathogenesis. Therefore, we aimed to determine if adiponectin is able to induce pro-inflammatory responses in cells involved in the pathogenesis of RA, but collected from subjects without any known inflammatory disease. PBMCs and FLS were obtained from non-inflamed subjects and stimulated with 5 μg/ml human recombinant adiponectin. Supernatants collected after 48 h were analyzed for the production of 13 chemokines and 12 cytokines using multiplex assay and ELISA. Adiponectin significantly stimulated the production of CXCL1, CXCL5, and interleukin (IL)-6 in both PBMCs and FLS, whereas it induced CCL20, CCL4, CCL3, CCL17, tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor and IL-10 only in PBMCs, and CXCL8, CXCL10, CCL5, CCL11, and CCL2 only in FLS. Pre-stimulation with TNF of FLS from non-inflamed subjects did not significantly enhance the release of most pro-inflammatory factors compared to adiponectin alone. Our findings indicate that PBMCs and FLS from non-inflamed subjects react to adiponectin stimulation with the secretion of several pro-inflammatory chemokines and cytokines. These results suggest that adiponectin is able to initiate pro-inflammatory responses in cells from non-inflamed subjects and support the hypothesis that adiponectin is implicated in the early phases of RA pathogenesis.

Dataset Information

Secretion of pro-inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast-like synoviocytes in juvenile idiopathic arthritis.

Purpose

Experimental design

Results

Conclusion and clinical relevance

Publications

Secretion of pro-inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast-like synoviocytes in juvenile idiopathic arthritis.

Similar Datasets

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