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Treatment with a CO-releasing molecule (CORM-3) reduces joint inflammation and erosion in murine collagen-induced arthritis
  1. M L Ferrandiz (luisa.ferrandiz{at}uv.es)
  1. University of Valencia, Spain
    1. N Maicas (nuriamaikas{at}hotmail.com)
    1. University of Valencia, Spain
      1. I Garcia-Arnandis (isabelgarcia2{at}hotmail.com)
      1. University of Valencia, Spain
        1. M C Terencio (carmen.terencio{at}uv.es)
        1. University of Valencia, Spain
          1. R Motterlini (r.motterlini{at}ic.ac.uk)
          1. Northwick Park Institute for Medical Research, United Kingdom
            1. I Devesa (i.devesa-giner{at}reuma.umcn.nl)
            1. Radboud University Nijmegen Medical Centre, Netherlands
              1. L A.B. Joosten (l.joosten{at}reuma.umcn.nl)
              1. Radboud University Nijmegen Medical Centre, Netherlands
                1. W B van den Berg (w.vandenberg{at}reuma.umcn.nl)
                1. Radboud University Nijmegen Medical Centre, Netherlands
                  1. M J Alcaraz (maria.j.alcaraz{at}uv.es)
                  1. University of Valencia, Spain

                    Abstract

                    Objective: CO-releasing molecules (CO-RMs) are a novel class of antiinflammatory agents. We have examined the possible therapeutic effects of CORM-3 in collagen-induced arthritis (CIA).

                    Methods: Arthritis was induced in DBA-1/J mice by type II collagen. Animals were treated with CORM-3 (5 and 10 mg/kg/day, intraperitoneally) or the inactive compound iCORM-3 (10 mg/kg/day, intraperitoneally) unable to release CO, from days 22 to 31. Production of anti-type II collagen antibodies, cytokines and cartilage olimeric matrix protein (COMP) was evaluated by enzyme-linked immunosorbent assay, and prostaglandin E2 (PGE2) by radioimmunoassay. Localization of cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and receptor activator of nuclear factor κB ligand (RANKL) was examined by immunohistochemistry.

                    Results: Therapeutic administration of CORM-3 suppressed both clinical and histopathological manifestations of disease. The levels of PGE2, interleukin(IL)-1β, IL-2, IL-6, IL-10 and tumor necrosis factor-α in joint tissues were inhibited by CORM-3. In contrast, this agent augmented IL-4. Anti-type II collagen antibodies and COMP levels in serum were reduced by CORM-3. Treatment with this agent decreased cellular infiltration, joint inflammation and destruction, as well as the expression of COX-2, ICAM-1 and RANKL, whereas HO-1 increased. These beneficial effects were due to CO release, as iCORM-3 was ineffective.

                    Conclusion: This study reveals the anti-arthritic properties of CORM-3 in the CIA model and supports the notion that CO-RMs could be developed as a novel strategy for the treatment of inflammatory and arthritic conditions.

                    • CO-releasing molecules
                    • antiinflammatory
                    • collagen-induced arthritis
                    • joint protection

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