caa a22 4500 445886196 CHVBK 20180317145600.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00011-011-0363-0 doi (NATIONALLICENCE)springer-10.1007/s00011-011-0363-0 Fibrinolysis is down-regulated in mouse collagen-induced arthritis, but its normalization does not alleviate the course of disease [Elektronische Daten] [Jakub Kwieciński, Elisabet Josefsson, Tao Jin] Objective: Down-regulation of fibrinolysis and increased fibrin deposition in joints are hallmarks of rheumatoid arthritis (RA), and are believed to be involved in disease progression. The mouse model of collagen-induced arthritis (CIA) closely resembles RA and has been used to explore mechanism and treatments of RA, but neither the fibrinolytic system nor pro-fibrinolytic therapies were investigated in CIA. Materials and methods: Plasmin activity, levels of plasminogen activator inhibitor (PAI-1), D-dimer, and IL-6 were measured in plasma of CIA mice. Fibrin deposition and PAI-1 levels were also measured in inflamed joints. Mice were treated with plasminogen activators uPA (urokinase-type plasminogen activator) or tPA (tissue-type plasminogen activator). Effects of treatment on disease severity and fibrinolytic system were assessed. Results: CIA caused decrease in plasmin activity, accompanied by increase in PAI-1 levels, in both blood and inflamed joints. This resulted in massive fibrin deposition in synovium. PAI-1 levels correlated negatively with plasmin activity and positively with IL-6. Treatments with uPA and tPA improved plasmin activity and removed fibrin deposits in inflamed joints. However, disease severity remained unchanged. Conclusions: Fibrinolytic changes in CIA parallel changes in RA, making CIA a suitable model to study fibrinolysis in RA. Normalization of plasmin activity in CIA after treatment with plasminogen activators had no effect on disease severity. Springer Basel AG, 2011 Rheumatoid arthritis nationallicence Collagen-induced arthritis nationallicence Fibrinolysis nationallicence Plasmin nationallicence tPA nationallicence uPA nationallicence Kwieciński Jakub Department of Rheumatology and Inflammation Research, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Box 480, 405-30, Gothenburg, Sweden aut Josefsson Elisabet Department of Rheumatology and Inflammation Research, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Box 480, 405-30, Gothenburg, Sweden aut Jin Tao Department of Rheumatology and Inflammation Research, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Box 480, 405-30, Gothenburg, Sweden aut Inflammation Research SP Birkhäuser Verlag Basel 60/11(2011-11-01), 1021-1029 1023-3830 60:11<1021 2011 60 11 https://doi.org/10.1007/s00011-011-0363-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0363-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kwieciński Jakub Department of Rheumatology and Inflammation Research, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Box 480, 405-30, Gothenburg, Sweden aut NATIONALLICENCE 700 1- Josefsson Elisabet Department of Rheumatology and Inflammation Research, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Box 480, 405-30, Gothenburg, Sweden aut NATIONALLICENCE 700 1- Jin Tao Department of Rheumatology and Inflammation Research, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Box 480, 405-30, Gothenburg, Sweden aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/11(2011-11-01), 1021-1029 1023-3830 60:11<1021 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer