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The Korean Association of Immunobiologists (대한면역학회)
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Expression and Function of Calcineurin in Inflammatory Arthritis

류마티스 관절염에서 칼시뉴린의 발현과 기능

  • Park, Bo-Hyoung (Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea) ;
  • Yoo, Seung-Ah (Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea) ;
  • Hong, Kyung-Hee (Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea) ;
  • Hyoung, Bok-Jin (Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea) ;
  • Hwang, Yu-Na (Department of Family Medicine, The Catholic University of Korea) ;
  • Cho, Chul-Soo (Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea) ;
  • Park, Won (Division of Rheumatology, Department of Internal Medicine, College of Medicine, Inha University) ;
  • Kim, Wan-Uk (Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea)
  • 박보형 (가톨릭대학교 의과대학 내과학교실 류마티스내과) ;
  • 유승아 (가톨릭대학교 의과대학 내과학교실 류마티스내과) ;
  • 홍경희 (가톨릭대학교 의과대학 내과학교실 류마티스내과) ;
  • 형복진 (가톨릭대학교 의과대학 내과학교실 류마티스내과) ;
  • 황유나 (가톨릭대학교 의과대학 가정의학과교실) ;
  • 조철수 (가톨릭대학교 의과대학 내과학교실 류마티스내과) ;
  • 박원 (인하대학교 의과대학 내과학교실 류마티스내과) ;
  • 김완욱 (가톨릭대학교 의과대학 내과학교실 류마티스내과)
  • Published : 2006.03.30
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Abstract

Background: Calcineurin plays a crucial role in T cell activation, cell growth, apoptosis, and angiogenesis, and its over-expression has been implicated in the pathogenesis of cardiomyopathy and stroke. However, the expression and function of calcineurin in the pathologic lesion of chronic inflammatory diseases, like rheumatoid synovium, remain to be defined. This study was aimed to determine the role of calcineurin in inflammatory arthritis and investigate the expression and function of calcineurin in the rheumatoid synovium and synoviocytes, the actual site of chronic inflammation. Methods: Immuno-histochemical staining using specific antibody to calcineurin was perfomed in the synovium of rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) from RA and osteoarthritis (OA) patients were isolated from RA and OA patients, and cultured with IL-1${\beta}$ and TNF-${\alpha}$ in the presence or absence of cyclosporin A, a calcineurin inhibitor. The calcineurin expression was assessed by phosphatase assay and Western blotting analysis. IL-6, -10, -17, matrix metalloproteinase (MMP)-1, -2, -3, and -9 released into the culture supernatants were measured by ELISA. After transfection with GFP-Cabin 1 gene into synoviocytes, the levels of IL-6 and MMPs were measured by ELISA. Results: Calcineurin was highly expressed in the lining layer of synovium and cultured synoviocytes of RA patients. The elevated calcineurin activity in the rheumatoid synoviocytes was triggered by proin flammatory cytokines such as IL-1${\beta}$ and TNF-${\alpha}$. In contrast, IL-10, an anti-inflammatory cytokine, failed to increase the calcineurin activity. The targeted inhibition of calcineurin by the over-expression of Cabin 1, a natural calcineurin antagonist, inhibited the production of IL-6 and MMP-2 by rheumatoid synoviocytes in a similar manner to the calcineurin inhibitor, cyclosporin A. Conclusion: These data suggest that abnormal activation of calcineurin in the synoviocytes may contribute to the pathogenesis of chronic arthritis, and thus provide a potential target for controlling inflammatory arthritis.

Keywords

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