Vol.21 No.3

Original Article

Therapeutic effect of D1-like dopamine receptor antagonist on collagen-induced arthritis of mice

Authors

Hiroki Nakashioya1.2,3 , Kazuhisa Nakano4 , Naoko Watanabe2 , Nobuyuki Miyasaka1 , Sho Matsushita4 , Hitoshi Kohsaka1,3

  • Global Center of Excellence (GCOE) Program, Department of Medicine and Rheumatology, Graduate School of Medical and Dental Sciences, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
  • Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1, Miyama, Funabashi Chiba, 274-8510, Japan
  • Clinical Immunology, RIKEN Research Center of Allergy and Immunology, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama Kanagawa, 230-0045, Japan
  • Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun Saitama, 350-0451, Japan
Received:

15 October 2010

Accepted:

14 November 2010

Published online:

28 December 2010

Full Text

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Abstract

Dopamine activates D1-like and D2-like receptors (D1R and D2R). While D1R antagonists have ameliorated the severity of disease in some experimental autoimmune models of mice by promoting interferon (IFN)-γ and inhibiting interleukin (IL)-17 production by T cells, dopamine effects in the immune system are reportedly diverse. To investigate the impact of D1R blockade on an animal model of rheumatoid arthritis (RA), DBA/1 mice with collagen-induced arthritis (CIA) were treated with a selective D1R antagonist, SCH23390, after the primary immunization. This treatment suppressed the severity of the CIA. Nevertheless, serum levels of antibodies to type II collagen were not affected by the treatment. Th1/Th17 differentiation of splenic T cells in the treated animals was not biased. In vitro, when bone marrow-derived macrophages were stimulated in the presence of the D1R antagonist SCH23390, alteration of inflammatory cytokine expression was not observed, but their in vitro differentiation to osteoclasts was inhibited. Co-administration of a selective D1R agonist, A68930, abrogated the in vivo anti-arthritic effect and the in vitro suppression of osteoclastogenesis by the D1R antagonist. Our results argue that D1R blockade is potentially a new approach to the treatment of RA. Its effect could be partly attributable to the inhibition of osteoclastogenesis.

Key words

Collagen-induced arthritis (CIA) - Dopamine - Osteoclast - Rheumatoid arthritis (RA)