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

Abstract

PurposeThe 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 designExpression 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.ResultsProtein 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 relevanceJIA 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.

Release kinetic of pro- and anti-inflammatory biomolecules from platelet-rich plasma and functional study on osteoarthritis synovial fibroblasts

“…Besides the classical catabolic/pro-inflammatory molecules (IL-1b, IL-6, IL-8) [19,20], most of the soluble factor we studied, such as chemokines, are less explored platelet-released molecules. They are involved in several physiopathological responses of joint tissues [21][22][23][24], and, similar to the preceding interleukins, they are more concentrated in L-PRP preparations.…”

T Cell Receptor-Independent, CD31/IL-17A-Driven Inflammatory Axis Shapes Synovitis in Juvenile Idiopathic Arthritis

“…The responsiveness of FLC to IL-17A was further examined by the addition of MnT2E, the biologics of TNFi and IL6i, or corticosteroid to the bioassays. Here, we focused on IL-17A-induced molecular effectors from experimental systems including those implicated in juvenile and adult arthritis ( 21 , 26 – 29 ). Out of 18 molecular effectors examined, 3 cytokines (TNFα, IL-6, and IL-1β) and 5 chemokines [CXCL1, CXCL8 (IL-8), CCL2 (MCP1), CCL3 (MIP1α), and CCL7 (MCP3)] were found to be significantly induced IL-17A (Figure 8 ).…”

“…After 24 h, CD38 expression was measured cytometrically, and the types and concentrations of soluble factors in the culture supernatant were examined by Luminex using a kit (LXSAHM18, R&D Systems). This kit consists of 18 molecules based on the global SF screening of de Jager et al ( 21 ) and reports about IL-17A-induced molecules in other experimental systems including adult arthritis ( 26 – 29 ).…”

Serum Interleukin-6 and CCL11/Eotaxin May Be Suitable Biomarkers for the Diagnosis of Chronic Nonbacterial Osteomyelitis

“…Indeed, IL-10 levels were slightly (but significantly) higher in CRMO patients when compared to healthy controls (but not other alternative diagnoses). This observation is not entirely surprising, since patients with other inflammatory diseases that are generally characterized by failure to express IL-10 from one or more cellular compartments may exhibit increased IL-10 serum levels when compared to healthy controls (e.g., oligoarticular JIA or systemic JIA) ( 21 – 26 ). Since CRMO is an inflammatory disorder and provided the fact that cells other than monocytes (e.g., lymphocytes, neutrophils, dendritic cells, eosinophils, etc., but also epithelia, stroma cells, etc.)…”