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J.Health Sci., 48(4), 354-358, 2002
Effects of Tumor Necrosis Factor-alpha on the Synthesis of DNA, the Secretion of Matrix Metalloproteinases/Tissue Inhibitors of Metalloproteinases, and the Activity of Invasive Migration in Cultured Vascular Smooth Muscle Cells
Toshiyuki Kaji,*, a Shouichi Hiraga,a Chika Yamamoto,a Yasuyuki Fujiwara,a Yoshimichi Ueda,b Fumiko Zisaki,b Kazushi Iwata,c Yasunori Okada,d and Shogo Katsudab
aDepartment of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan, bDepartment of Pathology, Kanazawa Medical University, Kahoku-gun, Ishikawa 920-0293, Japan, cBiopharmaceutical Department, Fuji Chemical Industries, Ltd., Takaoka, Toyama 933-8511, Japan, and dDepartment of Pathology, School of Medicine, Keio University, 35 Shinano-machi, Shinjyku-ku, Tokyo 160-8582, Japan
To address the question of whether or not tumor necrosis factor-alpha (TNF-alpha) regulates the functions of vascular smooth muscle cells (SMCs), dense or sparse cultures of the cells derived from human aorta were treated with TNF-alpha or TNF-alpha neutralizing antibody (TNF-alpha Ab). The incorporation of [3H]thymidine into the acid-insoluble fraction of SMCs was significantly inhibited by TNF-alpha, but stimulated by TNF-alpha Ab only when the cells had a high cell density. TNF-alpha significantly increased the accumulation of matrix metalloproteinase-1 and -3 (MMT-1 and -3, respectively) in the conditioned medium of dense SMCs, but does not affect that of tissue inhibitors of metalloproteinases-1 (TIMP-1); MMP-9 and TIMP-2 were undetectable. The invasive migration of SMCs determined by a Transwell system was stimulated by neither TNF-alpha nor TNF-alpha Ab. Taking these results together, it is suggested that TNF-alpha regulates DNA and MMP synthesis in dense SMCs but does not affect their invasive migration.
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