ORIGINAL ARTICLE
Inhibitory effect of mizoribine on matrix metalloproteinase-1 production in synovial fibroblasts and THP-1 macrophages
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Binbin Zhong1, Michiko Tajima1, Hidenari Takahara2, Hiromi Nochi3, Koichi Tamoto3, Naoto Tamura1 , Shigeto Kobayashi1, Yoshifumi Tamura4, Makoto Ikeda1, Tomohiro Akimoto1, Shinichi Yoshino5 and Hiroshi Hashimoto1
| (1) |
Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan |
| (2) |
Laboratory of Molecular Biology and Biochemistry, School of Agriculture, Ibaraki University, Inashiki, Ibaraki, Japan |
| (3) |
Department of Immunology and Microbiology, Faculty of Pharmaceutical Sciences, Health Sciences, University of Hokkaido, Ishikari-Toubetsu, Hokkaido, Japan |
| (4) |
Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan |
| (5) |
Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, Japan |
Received: 02 February 2005 Accepted: 18 May 2005
Abstract To investigate the mechanism of antirheumatic action of mizoribine (MZR), we examined the expression of matrix metalloproteinase-1 (MMP-1) and MMP-3 utilizing THP-1 derived macrophage-like cells (THP-1 macrophages) and human synovial fibroblasts (SFs). The cells were respectively stimulated with lipopolysaccharide (LPS) and interleukin-1β in the presence or absence of MZR in vitro. The concentrations of MMP-1 and MMP-3 in the supernatant were measured by enzyme-linked immunosorbent assay. The secretion of MMP-1 from SFs, as well as THP-1 macrophages, was inhibited by MZR in a dose-dependent manner. Furthermore, a quantitative real-time polymerase chain reaction revealed that MZR decreased the expression of MMP-1 messenger RNA. These findings may be an explanation for the clinical effect of MZR in patients with rheumatoid arthritis.
Key words Matrix metalloproteinase (MMP) - Mizoribine - Rheumatoid arthritis (RA) - Synovial fibroblast - THP-1 derived macrophage-like cells
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