Nitro-fatty acids decrease type I interferons and monocyte chemoattractant protein 1 in ex vivo models of inflammatory arthritis.

BACKGROUND: Inflammatory arthritis including rheumatoid arthritis (RA) and spondyloarthritis (SpA) is characterized by inflammation and destruction of the joints. Approximately one third of patients do not respond to first-line treatments. Nitro-fatty acids are bioactive lipids with anti-inflammatory properties and tissue-protective functions. The nitro-fatty acid 10-NO2-oleic acid (10-NO2-OA) is being tested in clinical trials for patients with fibrotic and inflammatory conditions. Here, we tested whether 10-NO2-OA could inhibit immune reactions involved in the inflammatory and joint destructive processes in inflammatory arthritis. METHODS: Synovial fluid and blood samples were obtained from 14 patients with active RA or SpA. The in vitro models consisted of synovial fluid mononuclear cells (SFMCs) cultured for 48 h, SFMCs cultured for 21 days, and fibroblast-like synovial cells (FLSs) co-cultured with peripheral blood mononuclear cells (PBMCs) for 48 h. Cells were treated with or without 10-NO2-OA or the tumor necrosis factor alpha (TNFα) inhibitor etanercept. Supernatants were analyzed for type I interferon, monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase 3 (MMP3) and tartrate resistant acid phosphatase (TRAP). RESULTS: In SFMCs cultured for 48 h, 10-NO2-OA dose-dependently decreased the secretion of bioactive type I interferons and MCP-1 but not MMP3 (P = 0.032, P = 0.0001, and P = 0.58, respectively). Both MCP-1 and MMP3 were decreased by etanercept (P = 0.0031 and P = 0.026, respectively). In SFMCs cultured for 21 days, 10-NO2-OA significantly decreased the production of MCP-1 but not TRAP (P = 0.027 and P = 0.1523, respectively). Etanercept decreased the production of TRAP but not MCP-1 (P < 0.001 and P = 0.84, respectively). In co-cultures of FLSs and PBMCs, 10-NO2-OA decreased the production of MCP-1 (P < 0.0001). This decrease in MCP-1 production was not seen with etanercept treatment (P = 0.47). CONCLUSION: 10-NO2-OA decreased the release of MCP-1 in three models of inflammatory arthritis. Of particular interest, 10-NO2-OA inhibited type I interferon, and 10-NO2-OA was more effective in reducing MCP-1 production in cultures dominated by FLSs compared with etanercept. Our results encourage clinical investigations of 10-NO2-OA in patients with inflammatory arthritis.

Structural, quantitative and functional comparison of amyloid P component in sera from patients with systemic lupus erythematosus and healthy donors.

Serum amyloid P component (SAP) is a serum protein that has a function as opsonin and is known to bind nuclear material with high affinity. Quantitative and/or qualitative deficiencies in SAP may possibly lead to the impairment of normal homoeostatic mechanisms of tissue turnover. Thus, SAP knockout mice display systemic lupus erythematosus (SLE)-like manifestations such as nephritis and circulating antinuclear antibodies. In the present study, we investigated whether there are changes in the structure, function or serum levels of SAP in serum from SLE patients as compared with those from healthy donors. We found that SAP in SLE sera has the same molecular mass as that of in the sera of normal individuals, when analysed by online immunoaffinity reversed phase mass spectrometry. Also, the serum levels of SAP did not differ significantly between the two groups. Finally, as an estimate of function, SAP from SLE patients appeared to have the same affinity for heparin and nucleosomes as SAP from normal individuals, when analysed by crossed affinity immunoelectrophoresis and enzyme-linked immunosorbent capture assay (ELISA). In conclusion, the data do not support alterations in the levels, structure or function of SAP circulating in SLE patients.