PMID- 34920714 OWN - NLM STAT- MEDLINE DCOM- 20220311 LR - 20220311 IS - 1471-2172 (Electronic) IS - 1471-2172 (Linking) VI - 22 IP - 1 DP - 2021 Dec 17 TI - Nitro-fatty acids decrease type I interferons and monocyte chemoattractant protein 1 in ex vivo models of inflammatory arthritis. PG - 77 LID - 10.1186/s12865-021-00471-3 [doi] LID - 77 AB - 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-NO(2)-oleic acid (10-NO(2)-OA) is being tested in clinical trials for patients with fibrotic and inflammatory conditions. Here, we tested whether 10-NO(2)-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-NO(2)-OA or the tumor necrosis factor alpha (TNFalpha) 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-NO(2)-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-NO(2)-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-NO(2)-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-NO(2)-OA decreased the release of MCP-1 in three models of inflammatory arthritis. Of particular interest, 10-NO(2)-OA inhibited type I interferon, and 10-NO(2)-OA was more effective in reducing MCP-1 production in cultures dominated by FLSs compared with etanercept. Our results encourage clinical investigations of 10-NO(2)-OA in patients with inflammatory arthritis. CI - (c) 2021. The Author(s). FAU - Hansen, A L AU - Hansen AL AD - Department of Biomedicine, Aarhus University, Hoegh-Guldbergs Gade 10, C. F. Mollers Alle 6, 8000, Aarhus C, Denmark. FAU - Rahbek, L S J AU - Rahbek LSJ AD - Department of Biomedicine, Aarhus University, Hoegh-Guldbergs Gade 10, C. F. Mollers Alle 6, 8000, Aarhus C, Denmark. FAU - Sorensen, A S AU - Sorensen AS AD - Department of Biomedicine, Aarhus University, Hoegh-Guldbergs Gade 10, C. F. Mollers Alle 6, 8000, Aarhus C, Denmark. FAU - Hundahl, M P AU - Hundahl MP AD - Department of Biomedicine, Aarhus University, Hoegh-Guldbergs Gade 10, C. F. Mollers Alle 6, 8000, Aarhus C, Denmark. FAU - Lomholt, S AU - Lomholt S AD - Department of Biomedicine, Aarhus University, Hoegh-Guldbergs Gade 10, C. F. Mollers Alle 6, 8000, Aarhus C, Denmark. FAU - Holm, C K AU - Holm CK AD - Department of Biomedicine, Aarhus University, Hoegh-Guldbergs Gade 10, C. F. Mollers Alle 6, 8000, Aarhus C, Denmark. FAU - Kragstrup, Tue W AU - Kragstrup TW AD - Department of Biomedicine, Aarhus University, Hoegh-Guldbergs Gade 10, C. F. Mollers Alle 6, 8000, Aarhus C, Denmark. kragstrup@biomed.au.dk. AD - Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark. kragstrup@biomed.au.dk. AD - Department of Rheumatology, Silkeborg Regional Hospital, Silkeborg, Denmark. kragstrup@biomed.au.dk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211217 PL - England TA - BMC Immunol JT - BMC immunology JID - 100966980 RN - 0 (10-nitro-oleic acid) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Chemokine CCL2) RN - 0 (Interferon Type I) RN - 0 (Oleic Acids) RN - OP401G7OJC (Etanercept) SB - IM MH - Adult MH - Anti-Inflammatory Agents/*metabolism MH - Arthritis, Rheumatoid/*metabolism MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Coculture Techniques MH - Etanercept/pharmacology MH - Female MH - Fibroblasts/*physiology MH - Humans MH - Interferon Type I/metabolism MH - Leukocytes, Mononuclear/*immunology MH - Male MH - Middle Aged MH - Oleic Acids/*metabolism MH - Spondylitis, Ankylosing/*metabolism MH - Synovial Fluid/*immunology PMC - PMC8684285 OTO - NOTNLM OT - Antirheumatic drug OT - Arthritis OT - Autoimmunity OT - Immunosuppressive drug OT - Inflammation OT - Nitro-fatty acid COIS- TWK has engaged in educational activities receiving speaking fees from Pfizer, Bristol-Myers Squibb, Eli Lilly, Novartis, and UCB and has been consultant and advisor for Bristol-Myers Squibb and Gilead. TWK is co-owner and clinical developer in iBiotech ApS developing diagnostic and therapeutic solutions for people with autoimmune diseases and cancer. The other authors have no competing interests. EDAT- 2021/12/19 06:00 MHDA- 2022/03/12 06:00 PMCR- 2021/12/17 CRDT- 2021/12/18 05:21 PHST- 2021/03/22 00:00 [received] PHST- 2021/12/02 00:00 [accepted] PHST- 2021/12/18 05:21 [entrez] PHST- 2021/12/19 06:00 [pubmed] PHST- 2022/03/12 06:00 [medline] PHST- 2021/12/17 00:00 [pmc-release] AID - 10.1186/s12865-021-00471-3 [pii] AID - 471 [pii] AID - 10.1186/s12865-021-00471-3 [doi] PST - epublish SO - BMC Immunol. 2021 Dec 17;22(1):77. doi: 10.1186/s12865-021-00471-3.