title: Tissue-specific expression of human calcineurin-binding protein 1 in mouse synovial tissue can suppress inflammatory arthritis.
abstract: Calcineurin (CN) is a calcium- and calmodulin-dependent serine/threonine phosphatase. In immune cells, CN controls the activity of a wide range of transcription factors, including nuclear factor of activated T, nuclear factor-kappa B, c-fos, and Elk-1. CN plays an important role in synoviocyte activation and arthritis progression in vivo and this function is tightly linked to dysregulated intracellular Ca(2+) store and Ca(2+) response triggered by proinflammatory cytokines. In the present study, transgenic mice expressing human calcineurin-binding protein 1 (hCabin1) were generated, driven by type II collagen promoter, and the efficiency of these mice was investigated by experimental arthritis. These transgenic mice successfully expressed hCabin1 in joint tissue as well as other organs such as liver, heart, and brain. The overexpression of hCabin1 reduced the disease severity during collagen-induced arthritis. In fibroblast-like synoviocytes (FLSs) from hCabin1 transgenic mice, the productions of these cytokines, including interleukin (IL)-2, IL-4, and IFN-γ, were decreased and matrix metalloproteinases were also depressed in transgenic mice FLS. In addition, these effects were only found in the joint tissue, which is a major inflammation site. These findings will provide a better knowledge of the pathogenic mechanisms of rheumatoid arthritis and a potential animal model of the chronic inflammatory conditions, including atherosclerosis and transplantation.
authors.affiliation: School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.forename: Jun Ku
authors.initials: JK
authors.lastname: Yi
authors.forename: Seo Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Hei Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Yuh
authors.forename: Ki Beom
authors.initials: KB
authors.lastname: Bae
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Ji
authors.forename: Hyun Shik
authors.initials: HS
authors.lastname: Lee
authors.forename: Sang Gyu
authors.initials: SG
authors.lastname: Lee
authors.forename: Yeon Sik
authors.initials: YS
authors.lastname: Choo
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Du Hak
authors.initials: du H
authors.lastname: Yoon
authors.forename: Byung Hwa
authors.initials: BH
authors.lastname: Hyun
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D016207:Cytokines; D020782:Matrix Metalloproteinases