Tissue-specific expression of human calcineurin-binding protein 1 in mouse synovial tissue can suppress inflammatory arthritis

Dong Hoon Yu, Jun Ku Yi, Seo Jin Park, Myoung Ok Kim, Hei Jung Kim, Hyung Soo Yuh, Ki Beom Bae, Young Rae Ji, Hyun Shik Lee, Sang Gyu Lee, Yeon Sik Choo, Jae Young Kim, Du Hak Yoon, Byung Hwa Hyun, Zae Young Ryoo

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 Ca2+ store and Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)6-11
Number of pages6
JournalJournal of Interferon and Cytokine Research
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2012

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