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

Autor: Carlos D. Rose, AnneMarie C. Brescia, Kathleen E. Sullivan, Megan M. Simonds
Rok vydání: 2017
Předmět:
Zdroj: PROTEOMICS - Clinical Applications. 11:1600088
ISSN: 1862-8346
DOI: 10.1002/prca.201600088
Popis: Objective The goal was 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. Methods Expression of 89 cytokines and chemokines was 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 were also examined for protein expression. Ingenuity Pathway Analysis (IPA) revealed top pathways and upstream regulators of significant proteins. Results Protein studies 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) were 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 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. This article is protected by copyright. All rights reserved
Databáze: OpenAIRE
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