title: A role for bradykinin in the development of anti-collagen antibody-induced arthritis.
abstract: OBJECTIVE
  Clinical and experimental observations have suggested that bradykinin, a major activation product of the plasma kallikrein-kinin system, is involved in the pathogenesis of arthritis, but the pathogenic role of bradykinin receptors remains inconclusive. In this study we examined whether bradykinin receptors are important in the pathogenesis of anti-collagen antibody-induced arthritis (CAIA) using double receptor-deficient (B1RB2R(-/-)) mice.
  
  
  METHODS
  CAIA was induced in B1RB2R(+/+) and B1RB2R(-/-) mice by injection of an anti-collagen antibody cocktail on day 0 and lipopolysaccharide on day 3. Severity of disease was evaluated by measurement of joint diameter and histological analysis. The expression of proinflammatory cytokines in joint tissue and peripheral mononuclear cells was determined by ELISA and real-time RT-PCR.
  
  
  RESULTS
  The absent expression of B1R and B2R mRNA in B1RB2R(-/-) mice was confirmed by RT-PCR. Although B1RB2R(+/+) mice developed severe CAIA, the severity of the disease was significantly attenuated in B1RB2R(-/-) mice. In B1RB2R(+/+) mice bearing CAIA, both B1R and B2R mRNA levels were increased in joint tissue and peripheral mononuclear cells. Compared with B1RB2R(+/+) mice, the production of IL-1β and IL-6 in joint tissue and their mRNA expression in peripheral mononuclear cells were remarkably reduced in B1RB2R(-/-) mice.
  
  
  CONCLUSIONS
  These observations provide genetic evidence that bradykinin plays an important role in the pathogenesis of CAIA. B1R, whose expression is induced in inflamed joint tissue and peripheral inflammatory cells, is important in the development of CAIA.
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Zhanli
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Jihong
authors.initials: J
authors.lastname: Dai
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Aizhen
authors.initials: A
authors.lastname: Yang
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA.Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA. yiwu@temple.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000009:adverse effects; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D001920:Bradykinin / Q000502:physiology*; D003094:Collagen / Q000009:adverse effects / Q000276:immunology; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007596:Joints / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018002:Receptors, Bradykinin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D053583:Interleukin-1beta; D015850:Interleukin-6; D018002:Receptors, Bradykinin; D003094:Collagen; D001920:Bradykinin
keywords: arthritis; bradykinin; cytokine; plasma kallikrein–kinin system