title: Fibrinolysis is down-regulated in mouse collagen-induced arthritis, but its normalization does not alleviate the course of disease.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Box 480, 405-30, Gothenburg, Sweden. jakub.kwiecinski@rheuma.gu.se
authors.forename: Jakub
authors.initials: J
authors.lastname: Kwieciński
authors.forename: Elisabet
authors.initials: E
authors.lastname: Josefsson
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy*; D003094:Collagen / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology; D005340:Fibrinogen / Q000737:chemistry; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D007150:Immunohistochemistry / Q000379:methods; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; C036309:fibrin fragment D; D005337:Fibrin; D005340:Fibrinogen; D003094:Collagen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator